Biochemistry, Genetics and Molecular Biology › Biochemistry

Lipid metabolism and biosynthesis

Works Count: 34071

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Description

This cluster of papers explores the diverse aspects of lipid metabolism, including the synthesis and storage of lipids in various organisms. It covers topics such as lipid droplets, triacylglycerol synthesis, adipose tissue lipolysis, glycerolipids, fatty acid biosynthesis, phospholipid metabolism, diacylglycerol acyltransferase, perilipin proteins, seed oil production, and chloroplast lipid biogenesis.

Keywords

Lipid Droplets; Triacylglycerol Synthesis; Adipose Tissue Lipolysis; Glycerolipids; Fatty Acid Biosynthesis; Phospholipid Metabolism; Diacylglycerol Acyltransferase; Perilipin Proteins; Seed Oil Production; Chloroplast Lipid Biogenesis

Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover.

1980-03-01

Akira Kishimoto , Yoshimi Takai , T Mori +2 more

greatly stimulated by the addition of diacylglycerol at less than 5% (w/w) the concentration of phospholipid.This stimulation was due to an increase in the apparent affinity of enzyme for phospholipid … greatly stimulated by the addition of diacylglycerol at less than 5% (w/w) the concentration of phospholipid.This stimulation was due to an increase in the apparent affinity of enzyme for phospholipid and to a concomitant decrease in the KO value for Ca2+ from about 1 X M to the micromolar range.Diacylglycerol alone showed little or no effect on enzymatic activity over a wide range of Ca2+ concentrations.This effect was greatest for diacylglycerol which contained unsaturated fatty acid at least at position 2. The active diacylglycerols so far tested included diolein, dilinolein, diarachidonin, 1-stearoyl-2-oleoyl diglyceride, and 1stearoyl-2-linoleoyl diglyceride.In contrast, diacylglycerols containing saturated fatty acids such as dipalmitin and distearin were far less effective.Triacyl-and monoacylglycerols were totally ineffective, irrespective of the fatty acyl moieties.Cholesterol and free fatty acids were also ineffective.Based on these obsewations, a possible coupling is proposed between the protein kinase activation and phosphatidylinositol turnover which can be provoked by various extracellular messengers.

Biochemistry of Lipids, Lipoproteins and Membranes

2021-01-01

Dennis E. Vance , Jean E. Vance

The Biochemistry and Molecular Biology of Lipid Accumulation in Oleaginous Microorganisms

2002-01-01

Colin Ratledge , James P. Wynn

Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets

1991-06-01

Andrew S. Greenberg , John J. Egan , Sheree A. Wek +3 more

The lipid fraction (fat cake) of rat epididymal adipocytes contains a prominent phosphoprotein (62 kDaapp by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) that is multiply phosphorylated by cAMP-dependent protein kinase in … The lipid fraction (fat cake) of rat epididymal adipocytes contains a prominent phosphoprotein (62 kDaapp by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) that is multiply phosphorylated by cAMP-dependent protein kinase in vivo, at which point it migrates as a 65/67-kDaapp doublet by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and is by far the most heavily radiolabeled protein in the cell. Western blot analysis of various tissues with immunopurified antibodies purified from antisera raised against the 62-kDa species suggests that the protein is specific for adipocytes. This protein, which we term perilipin, is found in differentiated cultured 3T3-L1 adipocytes, but not in their precursor 3T3-L1 fibroblasts. Immunocytochemical studies with specific antiserum shows that the perilipin is closely associated with the periphery of lipid storage droplets in cultured adipocytes. Given its adipocyte specificity, acute regulation by hormones, and subcellular location, we speculate that perilipin plays a role in the specialized lipid storage function of adipocytes.

Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.

1982-07-01

Marco Castagna , Yoshimi Takai , Kozo Kaibuchi +3 more

Tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) directly activate in vitro Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), which normally requires unsaturated diacylglycerol. Kinetic analysis indicates that TPA can substitute … Tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) directly activate in vitro Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), which normally requires unsaturated diacylglycerol. Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid. Under physiological conditions, the activation of this enzyme appears to be linked to the receptor-mediated phosphatidylinositol breakdown which may be provoked by a wide variety of extracellular messengers, eventually leading to the activation of specific cellular functions or proliferation. Using human platelets as a model system, TPA is shown to enhance the protein kinase C-specific phosphorylation associated with the release reaction in the total absence of phosphatidylinositol breakdown. Various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.

Transcriptional Regulation of Metabolism

2006-04-01

Béatrice Desvergne , Liliane Michalik , Walter Wahli

Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, … Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARγ in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.

Cloning of DGAT2, a Second Mammalian Diacylglycerol Acyltransferase, and Related Family Members

2001-10-01

Sylvaine Cases , Scot J. Stone , Ping Zhou +5 more

Studies involving the cloning and disruption of the gene for acyl-CoA:diacylglycerol acyltransferase (DGAT) have shown that alternative mechanisms exist for triglyceride synthesis. In this study, we cloned and characterized a … Studies involving the cloning and disruption of the gene for acyl-CoA:diacylglycerol acyltransferase (DGAT) have shown that alternative mechanisms exist for triglyceride synthesis. In this study, we cloned and characterized a second mammalian DGAT, DGAT2, which was identified by its homology to a DGAT in the fungus Mortierella rammaniana. DGAT2 is a member of a gene family that has no homology with DGAT1 and includes several mouse and human homologues that are candidates for additional DGAT genes. The expression of DGAT2 in insect cells stimulated triglyceride synthesis 6-fold in assays with cellular membranes, and DGAT2 activity was dependent on the presence of fatty acyl-CoA and diacylglycerol, indicating that this protein is a DGAT. Activity was not observed for acyl acceptors other than diacylglycerol. DGAT2 activity was inhibited by a high concentration (100 mm) of MgCl(2) in an in vitro assay, a characteristic that distinguishes DGAT2 from DGAT1. DGAT2 is expressed in many tissues with high expression levels in the liver and white adipose tissue, suggesting that it may play a significant role in mammalian triglyceride metabolism.

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Lipid Droplets Finally Get a Little R-E-S-P-E-C-T

2009-11-01

Robert V. Farese , Tobias C. Walther

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The biophysics and cell biology of lipid droplets

2013-11-13

Abdou Rachid Thiam , Robert V. Farese , Tobias C. Walther

Plant phenolic compounds and the isolation of plant enzymes

1966-05-01

W.David Loomis , J. Battaile

The biogenesis and functions of lipid bodies in animals, plants and microorganisms

2001-09-01

Denis J. Murphy

Fatty acid elongases in mammals: Their regulation and roles in metabolism

2006-03-07

Åsa Jakobsson , R.B. Westerberg , Anders Jacobsson

Rapid phosphatidic acid accumulation in response to low temperature stress in Arabidopsis is generated through diacylglycerol kinase

2013-01-01

Steven A. Arisz , Ringo van Wijk , Wendy Roels +3 more

Phosphatidic acid (PtdOH) is emerging as an important signalling lipid in abiotic stress responses in plants. The effect of cold stress was monitored using 32P-labelled seedlings and leaf discs of … Phosphatidic acid (PtdOH) is emerging as an important signalling lipid in abiotic stress responses in plants. The effect of cold stress was monitored using 32P-labelled seedlings and leaf discs of Arabidopsis thaliana. Low, non-freezing temperatures were found to trigger a very rapid 32P-PtdOH increase, peaking within 2 and 5 min, respectively. In principle, PtdOH can be generated through three different pathways, i.e. i) via de novo phospholipid biosynthesis (through acylation of lyso-PtdOH), ii) via phospholipase D hydrolysis of structural phospholipids or iii) via phosphorylation of diacylglycerol (DAG) by DAG kinase (DGK). Using a differential 32P-labelling protocol and a PLD-transphosphatidylation assay, evidence is provided that the rapid 32P-PtdOH response was primarily generated through DGK. A simultaneous decrease in the levels of 32P-PtdInsP, correlating in time, temperature dependency and magnitude with the increase in 32P-PtdOH, suggested that a PtdInsP-hydrolyzing PLC generated the DAG in this reaction. Testing T-DNA insertion lines available for the seven DGK genes, revealed no clear changes in 32P-PtdOH responses, suggesting functional redundancy. Similarly, known cold-stress mutants were analyzed to investigate whether the PtdOH response acted downstream of the respective gene products. The hos1, los1 and fry1 mutants were found to exhibit normal PtdOH responses. Slight changes were found for ice1, snow1, and the overexpression line Super-ICE1, however, this was not cold-specific and likely due to pleiotropic effects. A tentative model illustrating direct cold effects on phospholipid metabolism is presented.

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Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis

2008-08-30

Chi‐Liang Eric Yen , Scot J. Stone , Suneil K. Koliwad +2 more

Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, … Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases.

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Structure of human pancreatic lipase

1990-02-01

F.K. Winkler , A. D’Arcy , Willi Hunziker

The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice

2009-12-17

Hervé Guillou , Damir Zadravec , Pascal G.P. Martin +1 more

Profiling Membrane Lipids in Plant Stress Responses

2002-08-01

Ruth Welti , Weiqi Li , Maoyin Li +6 more

Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis

2007-09-19

Dawn Brasaemle

The majority of eukaryotic cells synthesize neutral lipids and package them into cytosolic lipid droplets. In vertebrates, triacylglycerol-rich lipid droplets of adipocytes provide a major energy storage depot for the … The majority of eukaryotic cells synthesize neutral lipids and package them into cytosolic lipid droplets. In vertebrates, triacylglycerol-rich lipid droplets of adipocytes provide a major energy storage depot for the body, whereas cholesteryl ester-rich droplets of many other cells provide building materials for local membrane synthesis and repair. These lipid droplets are coated with one or more of five members of the perilipin family of proteins: adipophilin, TIP47, OXPAT/MLDP, S3-12, and perilipin. Members of this family share varying levels of sequence similarity, lipid droplet association, and functions in stabilizing lipid droplets. The most highly studied member of the family, perilipin, is the most abundant protein on the surfaces of adipocyte lipid droplets, and the major substrate for cAMP-dependent protein kinase [protein kinase A (PKA)] in lipolytically stimulated adipocytes. Perilipin serves important functions in the regulation of basal and hormonally stimulated lipolysis. Under basal conditions, perilipin restricts the access of cytosolic lipases to lipid droplets and thus promotes triacylglycerol storage. In times of energy deficit, perilipin is phosphorylated by PKA and facilitates maximal lipolysis by hormone-sensitive lipase and adipose triglyceride lipase. A model is discussed whereby perilipin serves as a dynamic scaffold to coordinate the access of enzymes to the lipid droplet in a manner that is responsive to the metabolic status of the adipocyte.

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Fatty acid unsaturation, mobilization, and regulation in the response of plants to stress

2008-01-28

Robert G. Upchurch

Triglyceride accumulation protects against fatty acid-induced lipotoxicity

2003-03-10

Laura L. Listenberger , Xianlin Han , Sarah E. Lewis +4 more

Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common … Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis. Moreover, in the setting of impaired triglyceride synthesis, oleate induces lipotoxicity. Our findings support a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation.

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Rapid Preparation of Fatty Acid Esters from Lipids for Gas Chromatographic Analysis.

1966-03-01

L. Metcalfe , Alexa Schmitz , J. R. Pelka

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRapid Preparation of Fatty Acid Esters from Lipids for Gas Chromatographic Analysis.L. D. Metcalfe, A. A. Schmitz, and J. R. PelkaCite this: Anal. Chem. 1966, 38, 3, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRapid Preparation of Fatty Acid Esters from Lipids for Gas Chromatographic Analysis.L. D. Metcalfe, A. A. Schmitz, and J. R. PelkaCite this: Anal. Chem. 1966, 38, 3, 514–515Publication Date (Print):March 1, 1966Publication History Published online1 May 2002Published inissue 1 March 1966https://doi.org/10.1021/ac60235a044Request reuse permissionsArticle Views5369Altmetric-Citations1800LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (289 KB) Get e-Alertsclose Get e-Alerts

Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis

1998-10-27

Sylvaine Cases , Steven J. Smith , Yao-Wu Zheng +7 more

Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20 ) catalyzes the terminal and only committed step in triacylglycerol synthesis, … Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20 ) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined; during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation.

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Fatty Acid Trafficking in Starved Cells: Regulation by Lipid Droplet Lipolysis, Autophagy, and Mitochondrial Fusion Dynamics

2015-03-01

Angelika S. Rambold , Sarah Cohen , Jennifer Lippincott‐Schwartz

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Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat

2000-05-01

Steven J. Smith , Sylvaine Cases , Dalan R. Jensen +7 more

Lipid extraction of tissues with a low-toxicity solvent

1978-10-01

Atsushi Hara , Norman S. Radin

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Regulation of Hepatic Lipogenesis by the Transcription Factor XBP1

2008-06-12

Ann–Hwee Lee , Erez Scapa , David E. Cohen +1 more

Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded … Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.

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The lipid droplet is an important organelle for hepatitis C virus production

2007-08-26

Yusuke Miyanari , Kimie Atsuzawa , Nobuteru Usuda +7 more

Phospholipid:diacylglycerol acyltransferase: An enzyme that catalyzes the acyl-CoA-independent formation of triacylglycerol in yeast and plants

2000-05-30

Anders Dahlqvist , Ulf Ståhl , Marit Lenman +5 more

Triacylglycerol (TAG) is known to be synthesized in a reaction that uses acyl-CoA as acyl donor and diacylglycerol (DAG) as acceptor, and which is catalyzed by the enzyme acyl-CoA:diacylglycerol acyltransferase. … Triacylglycerol (TAG) is known to be synthesized in a reaction that uses acyl-CoA as acyl donor and diacylglycerol (DAG) as acceptor, and which is catalyzed by the enzyme acyl-CoA:diacylglycerol acyltransferase. We have found that some plants and yeast also have an acyl-CoA-independent mechanism for TAG synthesis, which uses phospholipids as acyl donors and DAG as acceptor. This reaction is catalyzed by an enzyme that we call phospholipid:diacylglycerol acyltransferase, or PDAT. PDAT was characterized in microsomal preparations from three different oil seeds: sunflower, castor bean, and Crepis palaestina. We found that the specificity of the enzyme for the acyl group in the phospholipid varies between these species. Thus, C. palaestina PDAT preferentially incorporates vernoloyl groups into TAG, whereas PDAT from castor bean incorporates both ricinoleoyl and vernoloyl groups. We further found that PDAT activity also is present in yeast microsomes. The substrate specificity of this PDAT depends on the head group of the acyl donor, the acyl group transferred, and the acyl chains of the acceptor DAG. The gene encoding the enzyme was identified. The encoded PDAT protein is related to lecithin:cholesterol acyltransferase, which catalyzes the acyl-CoA-independent synthesis of cholesterol esters. However, budding yeast PDAT and its relatives in fission yeast and Arabidopsis form a distinct branch within this protein superfamily, indicating that a separate PDAT enzyme arose at an early point in evolution.

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Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O

1992-07-01

J. L. Ram�rez-Zacar�as , F. Castro-Mu�ozledo , Walid Kuri‐Harcuch

Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome

2006-05-01

Achim Lass , Robert Zimmermann , Guenter Haemmerle +7 more

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DESATURATION AND RELATED MODIFICATIONS OF FATTY ACIDS

1998-06-01

John Shanklin , Edgar B. Cahoon

▪ Abstract Desaturation of a fatty acid first involves the enzymatic removal of a hydrogen from a methylene group in an acyl chain, a highly energy-demanding step that requires an … ▪ Abstract Desaturation of a fatty acid first involves the enzymatic removal of a hydrogen from a methylene group in an acyl chain, a highly energy-demanding step that requires an activated oxygen intermediate. Two types of desaturases have been identified, one soluble and the other membrane-bound, that have different consensus motifs. Database searching for these motifs reveals that these enzymes belong to two distinct multifunctional classes, each of which includes desaturases, hydroxylases, and epoxidases that act on fatty acids or other substrates. The soluble class has a consensus motif consisting of carboxylates and histidines that coordinate an active site diiron cluster. The integral membrane class contains a different consensus motif composed of histidines. Biochemical and structural similarities between the integral membrane enzymes suggest that this class also uses a diiron cluster for catalysis. Soluble and membrane enzymes have been successfully re-engineered for substrate specificity and reaction outcome. It is anticipated that rational design of these enzymes will result in new and desired activities that may form the basis for improved oil crops.

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Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase

2004-11-18

Robert Zimmermann , Juliane Gertrude Bogner‐Strauß , Guenter Haemmerle +7 more

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until … Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.

FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling

2012-03-01

Rudolf Zechner , Robert Zimmermann , Thomas O. Eichmann +4 more

Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed … Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. New findings that lipolytic products and intermediates participate in cellular signaling processes and that "lipolytic signaling" is particularly important in many nonadipose tissues unveil a previously underappreciated aspect of lipolysis, which may be relevant for human disease.

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Quantitative Determination of Serum Triglycerides by the Use of Enzymes

1973-05-01

Giovanni Bucolo , H David

Abstract We describe a novel method for determining serum triglycerides, in which an enzymatic hydrolysis replaces the more commonly used saponification procedure. Under the conditions of the assay, the enzymatic … Abstract We describe a novel method for determining serum triglycerides, in which an enzymatic hydrolysis replaces the more commonly used saponification procedure. Under the conditions of the assay, the enzymatic hydrolysis can be completed in less than 10 min by the combined action of a microbial lipase and a protease. We have been able to demonstrate complete hydrolysis of triglycerides by thin-layer chromatography of the reaction products, by recovery of glycerol from sera of known triglycerides content, and by comparison of triglyceride assays on a number of sera assayed by our method vs. the AutoAnalyzer procedure. The hydrolysis is directly coupled to the enzymatic determination of glycerol, and is followed through absorbance changes at 340 nm. The assay is simple, rapid, and requires only 50 µl or less of sample. Because the enzymes used do not release glycerol from other compounds in serum, the hydrolysis can be considered specific for triglycerides.

Lipid Droplets and Cellular Lipid Metabolism

2012-05-22

Tobias C. Walther , Robert V. Farese

Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores metabolic energy and membrane components, making … Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores metabolic energy and membrane components, making LDs hubs for lipid metabolism. In addition, LDs are implicated in a number of other cellular functions, ranging from protein storage and degradation to viral replication. These processes are functionally linked to many physiological and pathological conditions, including obesity and related metabolic diseases. Despite their important functions and nearly ubiquitous presence in cells, many aspects of LD biology are unknown. In the past few years, the pace of LD investigation has increased, providing new insights. Here, we review the current knowledge of LD cell biology and its translation to physiology.

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Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis

2009-12-18

Daniel K. Nomura , Jonathan Z. Long , Sherry Niessen +3 more

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Enzymes of triacylglycerol synthesis and their regulation

2003-09-16

Rosalind Coleman

A simple procedure for rapid transmethylation of glycerolipids and cholesteryl esters

1982-09-01

William W. Christie

A simple procedure suitable for rapid transmethylation of triacylglycerols, other neutral lipids (including cholesteryl esters), and glycerophospholipids is described.Lipids in diethyl ether solution (50 volumes), in the presence of methyl … A simple procedure suitable for rapid transmethylation of triacylglycerols, other neutral lipids (including cholesteryl esters), and glycerophospholipids is described.Lipids in diethyl ether solution (50 volumes), in the presence of methyl acetate (1 vol), are reacted with 1 M sodium methoxide in methanol (1 vol) at room temperature.Essentially complete transmethylation can occur within a few minutes with no hydrolysis.Glassware and reagent requirements are minimal and samples are ready for gas-liquid chromatography analysis with very little work-up.-Christie,W. W. A simple procedure for rapid transmethylation of glycerolipids and cholesteryl esters.

mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway

2011-08-01

Timothy R. Peterson , Shomit Sengupta , Thurl E. Harris +7 more

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STRUCTURE, FUNCTION, AND DIETARY REGULATION OF Δ6, Δ5, AND Δ9 DESATURASES

2004-06-09

Manabu Nakamura , Takayuki Nara

Fatty acid desaturases introduce a double bond in a specific position of long-chain fatty acids, and are conserved across kingdoms. Degree of unsaturation of fatty acids affects physical properties of … Fatty acid desaturases introduce a double bond in a specific position of long-chain fatty acids, and are conserved across kingdoms. Degree of unsaturation of fatty acids affects physical properties of membrane phospholipids and stored triglycerides. In addition, metabolites of polyunsaturated fatty acids are used as signaling molecules in many organisms. Three desaturases, Delta9, Delta6, and Delta5, are present in humans. Delta-9 catalyzes synthesis of monounsaturated fatty acids. Oleic acid, a main product of Delta9 desaturase, is the major fatty acid in mammalian adipose triglycerides, and is also used for phospholipid and cholesteryl ester synthesis. Delta-6 and Delta5 desaturases are required for the synthesis of highly unsaturated fatty acids (HUFAs), which are mainly esterified into phospholipids and contribute to maintaining membrane fluidity. While HUFAs may be required for cold tolerance in plants and fish, the primary role of HUFAs in mammals is cell signaling. Arachidonic acid is required as substrates for eicosanoid synthesis, while docosahexaenoic acid is required in visual and neuronal functions. Desaturases in mammals are regulated at the transcriptional level. Reflecting overlapping functions, three desaturases share a common mechanism of a feedback regulation to maintain products in membrane phospholipids. At the same time, regulation of Delta9 desaturase differs from Delta6 and Delta5 desaturases because its products are incorporated into more diverse lipid groups. Combinations of multiple transcription factors achieve this sophisticated differential regulation.

Lipidomics reveals a remarkable diversity of lipids in human plasma

2010-07-30

Oswald Quehenberger , Aaron M. Armando , Alex Brown +7 more

The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis … The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules. The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules. In this era of genomics, transcriptomics, and proteomics, metabolomics is emerging as an important component of the omics evolution (1Dennis E.A. Lipidomics joins the omics evolution.Proc. Natl. Acad. Sci. USA. 2009; 106: 2089-2090Crossref PubMed Scopus (119) Google Scholar). Of the four kinds of biological molecules that comprise the human body, i.e., nucleic acids, amino acids (proteins), carbohydrates (sugars), and lipids (fats), lipids stand out among the various cellular metabolites in the sheer number of distinct molecular species. Using state-of-the-art lipidomics approaches made possible by newly developed instrumentation, protocols, and bioinformatics tools (2Lipidomics and Bioactive Lipids: Mass-Spectrometry-Based Lipid Analysis.Methods Enzymol. 2007; 43: 1-387Google Scholar), the LIPID MAPS Consortium is carrying out comprehensive analyses of the mammalian lipidome (3Dennis E.A. Brown H.A. Deems R.A. Glass C.K. Merrill A.H. Murphy R.C. Raetz R.H. Shaw W. Subramaniam S. Russel D.W. et al.The LIPID MAPS approach to lipidomics.in: Feng L. Prestwich G. Functional Lipidomics. CRC Press/Taylor & Francis Group, Boca Raton, FL2005Crossref Google Scholar). As an emerging 'omics' field, lipidomics provides a powerful approach to understanding lipid biology (4Brown H.A. Murphy R.C. Working towards an exegesis for lipids in biology.Nat. Chem. Biol. 2009; 5: 602-606Crossref PubMed Scopus (114) Google Scholar). The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the National Institute of Standards (NIST) recently produced a human plasma standard reference material (SRM 1950) for metabolite analysis. The SRM was prepared by obtaining plasma samples from 100 individuals between 40 and 50 years of age, whose ethnicity was representative of the US population and that included an equal number of men and women. The intent of the NIDDK/NIST project was to provide a reference material that would be publically available to researchers and that could be used by the clinical chemistry community to identify plasma metabolites for diagnostic purposes. 3Further information is available at www.nist.gov/cstl/analytical/organic/metabolitesinserum.cfm Signature metabolites could then be further probed for their usefulness as disease biomarkers. The LIPID MAPS Consortium has developed innovative lipidomics techniques based on liquid chromatography coupled to mass spectroscopy to probe biological systems (3Dennis E.A. Brown H.A. Deems R.A. Glass C.K. Merrill A.H. Murphy R.C. Raetz R.H. Shaw W. Subramaniam S. Russel D.W. et al.The LIPID MAPS approach to lipidomics.in: Feng L. Prestwich G. Functional Lipidomics. CRC Press/Taylor & Francis Group, Boca Raton, FL2005Crossref Google Scholar) and has undertaken the task of analyzing the NIDDK/NIST SRM by systematically identifying and quantifying the lipid molecular species of the mammalian lipidome (5Fahy E. Subramaniam S. Brown H.A. Glass C.K. Merrill Jr, A.H. Murphy R.C. Raetz C.R. Russell D.W. Seyama Y. Shaw W. et al.A comprehensive classification system for lipids.J. Lipid Res. 2005; 46: 839-861Abstract Full Text Full Text PDF PubMed Scopus (1166) Google Scholar, 6Fahy E. Subramaniam S. Murphy R.C. Nishijima M. Raetz C.R. Shimizu T. Spener F. van Meer G. Wakelam M.J. Dennis E.A. Update of the LIPID MAPS comprehensive classification system for lipids.J. Lipid Res. 2009; 50: S9-S14Abstract Full Text Full Text PDF PubMed Scopus (1090) Google Scholar). We report here for the first time an in-depth lipid profile of human plasma that reveals the enormous structural diversity of lipids comprising the six major lipid categories as defined by LIPID MAPS. 4See the LIPID MAPS/Nature Lipidomics Gateway, www.lipidmaps.org Lipidomics analysis of the sample was challenging due to the extremely large number of lipid species in human plasma and the analytical complexity of the molecular species present. Nevertheless, we report the quantitative levels of over 500 different lipid molecular species present in this human reference plasma sample. Experimental details are provided online as supplemental material. The results are presented and discussed below for each main lipid category and the diversity of lipid molecular species is summarized in Fig. 1. The most number of lipid molecular species analyzed was for the sphingolipid category but the sterols, including cholesterol and its esters, were the most abundant of the lipids on a molar basis (nmol/ml) followed by triglycerides, glycerophospholipids, free fatty acyls, sphingolipids, diacylglycerols, and prenols, though on a weight basis (mg/dl) the glycerophospholipids were the most abundant, as shown in Table 1. Complete data sets are also available on the LIPID MAPS/Nature Lipidomics Gateway, www.lipidmaps.org.TABLE 1.Lipid categories and species quantified in the human plasma SRMLipid CategoryNumber of SpeciesSum (nmol/ml)Sum (mg/dl)Fatty Acyls Fatty Acids312145.82 Eicosanoids760.0710.002Total1072145.82Glycerolipids Triacylglycerols18105890.6 1,2-Diacylglycerols28392.36 1,3-Diacylglycerols27130.805Total73111093.7Glycerophospholipids PE3843532.7 LPE736.61.78 PC311974157 LPC121035.25 PS207.000.559 PG166.120.480 PA152.500.173 PI1931.52.74 N-acyl-PS20.0130.001Total1602596201Sphingolipids Sphingomyelins101303.46822.817 Monohexosylceramides562.31350.180 Ceramides4111.5860.732 Sphingoid Bases60.56780.02029Total20431823.7Sterol Lipids∗Sterols in plasma (nmol/ml) were determined as described in the supplementary experimental procedures. Weight calculations (mg/dl) were based on the sterol backbone for sterol esters. Additionally, total sterols were also measured by clinical laboratories following procedures certified by the Center for Disease Control and they reported similar plasma levels, though they are lower than the national average (National Health and Nutrition Examination Survey 2003–2006). The SRM consists of plasma pooled from individuals within a narrow age range. Thus, cholesterol values may deviate from other averages that include individuals from a wider age spectrum. Free Sterols1482631.8 Esterified Sterols222954114Total363780146Prenol Lipids Dolichols60.0250.003 Coenzyme-Q24.590.394Total84.620.397Total5888023471∗ Sterols in plasma (nmol/ml) were determined as described in the supplementary experimental procedures. Weight calculations (mg/dl) were based on the sterol backbone for sterol esters. Additionally, total sterols were also measured by clinical laboratories following procedures certified by the Center for Disease Control and they reported similar plasma levels, though they are lower than the national average (National Health and Nutrition Examination Survey 2003–2006). The SRM consists of plasma pooled from individuals within a narrow age range. Thus, cholesterol values may deviate from other averages that include individuals from a wider age spectrum. Open table in a new tab Several simplifying assumptions were necessary to generate the data in the molecular detail presented throughout this study. First, only a small number of isotope-labeled internal and reference standards are available for mass spectrometry-based quantitative analyses for the most abundant lipids in plasma, i.e., cholesteryl esters, triglycerides, and glycerophospholipids. Therefore, we assumed that the behavior of these standards with respect to extraction and mass spectrometry was representative for each class of abundant lipid. Second, for the triglycerides and glycerophospholipids, isobaric (same molecular weight) molecular species exist, which further confounds precise quantitation. We realize that these simplifying assumptions may have introduced errors into the accuracy with respect to absolute quantitation for each lipid species. Nonetheless, the total values obtained for individual lipid classes are similar to those measured by techniques that disregard molecular species identity. The information provided in the supplementary tables thus provides an accurate picture of the relative amounts of unique lipid molecular species in the NIST plasma sample. When using the data as a reference, one should keep in mind that the plasma samples were kept frozen for some time during the collection effort. Although every precaution was taken to minimize the effects of storage and thawing on the integrity of the sample, some oxidation or hydrolysis of lipids cannot be entirely ruled out. Physical strain imposed during the process of blood drawing may lead to the activation of leukocytes and induce the formation of metabolites of the arachidonic acid cascade. This may potentially contribute to the amount of eicosanoids that were measured in the plasma samples. Leukocyte activation is of particular concern when hemolysis occurs; therefore, all individual plasma samples that displayed visible indications of hemolysis were discarded and not included to generate the pool of the plasma SRM. Although free fatty acids represent only a small fraction of total fatty acids in plasma, they represent a highly metabolically active lipid class. Adipose tissue is the main source of plasma free fatty acids, which have a distribution that is closely related to the fatty acid composition of the diet (7Hertzel A.V. Thompson B.R. Wiczer B.M. Bernlohr D.A. Lipid metabolism in adipose tissue.in: Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins and Membranes. Elsevier, Amsterdam2008: 277-304Crossref Scopus (5) Google Scholar). Under normal conditions the release of fatty acids from adipose tissue is tightly regulated to meet the energy demands of tissues; however, in several metabolic disorders this homeostasis is compromised and shifts toward increased lipolysis leading to the release of excess free fatty acids relative to tissue needs. As shown in Table 1 and supplementary Table IA, human plasma of healthy individuals after overnight fasting contains an average of 214 nmol/ml of free fatty acids. Oleic acid (18:1) is the major constituent followed by palmitic acid (16:0) and stearic acid (18:0) (supplementary Table IA). Together, these three species comprise about 78% of all free fatty acids in the circulation. Linoleic acid (18:2) and arachidonic acid (20:4) are the main PUFAs (about 8% of the total), but the nutritionally essential α-linolenic acid (18:3ω-3), eicosapentaenoic acid (20:5, EPA), and docosahexaenoic acid (22:6, DHA) are also present at significant levels, together making up about 1% of all free fatty acids. Eicosanoids are a class of bioactive lipid mediators that are derived from the metabolism of arachidonic acid or related PUFAs (8Funk C.D. Prostaglandins and leukotrienes: advances in eicosanoid biology.Science. 2001; 294: 1871-1875Crossref PubMed Scopus (3070) Google Scholar). Three classes of enzymes including cyclooxygenases (COX-1 and COX-2), lipoxygenases (LOXs), and cytochrome P450 epoxygenases (CYPs) synthesize eicosanoids (9Buczynski M.W. Dumlao D.S. Dennis E.A. Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology.J. Lipid Res. 2009; 50: 1015-1038Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar). In addition, PUFAs can undergo autoxidation to produce bioactive lipids through a nonenzymatic pathway. PUFA metabolites derived from all three enzymatic pathways and through autoxidation and lipid peroxidation were detected in the SRM (Table 1 and supplementary Table IB). Typically, eicosanoids have a short half-life and undergo further enzymatic or nonenzymatic modifications that are often accompanied by a change of pharmacological potency. Notably, 15deoxy Δ12,14 PGD2 (15d PGD2), a degradation product of prostaglandin D2 (PGD2), was one of the major COX metabolites found in the human plasma sample. The formation of 15d PGD2 is of particular interest because, like 15deoxy Δ12,14 PGJ2 (15d PGJ2), this eicosanoid robustly stimulates peroxisome proliferator-activated receptor-γ activity, which has been implicated in the regulation of inflammatory responses. The hydroxylated products of arachidonic acid, 5-hydroxy-eicosatetraenoic acid (5-HETE) and 12-HETE, and of linoleic acid, 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE, were the major metabolites of the LOX pathway detected in the sample. In fact, the 5-LOX product 5-HETE represented the single most prominent eicosanoid found in the SRM. We also identified some prominent metabolites derived from the CYP pathway including 12,13-dihydroxy-octadec-9-enoic acid (12,13 DiHOME), which is produced by the action of epoxide hydrolase from the corresponding 12,13 epoxide of linoleic acid, the epoxide 14,15-epoxy-5,8,11-eicosatrienoic acid (14,15 EpETrE) formed from arachidonic acid and the corresponding vicinal diol 14,15-dihydroxy-5,8,11-eicosatrienoic acid (14,15 DiHETrE). Some autoxidation products were also detected. Interestingly, the majority of these lipid peroxidation products are derived from DHA, even though this 22:6 fatty acid represents a minor fraction of all free PUFAs in the plasma. Glycerolipids encompassed a high proportion of total lipids present in plasma. Of these, the most abundant members were triacylglycerols (TAGs), which were present at a concentration of 1.1 µmol/ml (90.6 mg/dl) in the plasma SRM (Table 1). The absolute concentration of TAGs is dependent on food intake because the synthesis and packaging of TAG into lipoprotein particles (chiefly chylomicrons and very low density lipoprotein) is the major mechanism by which these lipids are distributed to tissues in the body. We found that about 50% of all TAGs had a total of 52 fatty acyl carbon atoms and that most fatty acyl groups had multiple double bonds. Although the analysis of TAGs did not allow definition of all molecular species, previous studies have revealed that each molecular subset (e.g., 52:3 TAG) is a complex mixture of multiple isobaric entities (10McAnoy A.M. Wu C.C. Murphy R.C. Direct qualitative analysis of triacylglycerols by electrospray mass spectrometry using a linear ion trap.J. Am. Soc. Mass Spectrom. 2005; 16: 1498-1509Crossref PubMed Scopus (152) Google Scholar). For example, the three abundant species that make up 52:3 TAG are 16:1/18:1/18:1, 16:1/18:0/18:2, and 16:0/18:1/18:2, not considering isomers that differ at the position on the glycerol carbon atoms where acylation occurs. Including minor fatty acyl species such as 18:3, 20:1, 20:2, and 20:3 fatty acids in the calculation expands the number of possible nonisomeric and distinct molecular species to over seven. Applying chromatographic retention times and considering all isobaric species, it was possible to detect over 200 individual molecular species of TAGs in the plasma sample (supplementary Table IIA). In addition, several ether-linked glycerolipids were detected as alkylether triacylglycerols (ether 50:3, ether 50:2, ether 52:4, ether 52:3, ether 54:6, ether 54:5, and ether 54:4). Diacylglycerols (DAGs) were also present in the plasma sample but at substantially lower levels. Both 1,2-DAGs (supplementary Table IIB) and 1,3-DAGs (supplementary Table IIC) were quantified and found to contain between 30 and 40 total acyl carbon atoms esterified to the glycerol backbone. 1,2-DAGs were about three times as abundant as 1,3-DAGs in this sample. Over 200 species of glycerophospholipids were detected and identified in the plasma SRM. Due to the presence of isobaric species with the same m/z, out of all species identified, 158 glycerophosphate (PA), glycerophosphocholine (PC), glycerophosphoethanolamine (PE), glycerophosphoglycerol (PG), glycerophosphoinositol (PI), and glycerophosphoserine (PS) species were quantified and are summarized in Table 1. The composition by subclass and quantities of individual glycerophospholipid species are reported in supplementary Table IIIA. By mass, the overwhelming majority of glycerophospholipids in human plasma are PCs and PEs. These two classes were also found to contain substantial amounts of ether-linked lipids (PEe/ p = 43% of PE by mass; PCe/p = 5.4% of PC by mass; e designates the plasmanyl and p designates the plasmenyl analogues of glycerophospholipids). The amount of total glycerophospholipid is similar to that previously reported using different analytical approaches (11Dougherty R.M. Galli C. Ferro-Luzzi A. Iacono J.M. Lipid and phospholipid fatty acid composition of plasma, red blood cells, and platelets and how they are affected by dietary lipids: a study of normal subjects from Italy, Finland, and the USA.Am. J. Clin. Nutr. 1987; 45: 443-455Crossref PubMed Scopus (266) Google Scholar, 12Bradamante S. Barchiesi E. Barenghi L. Zoppi F. An alternative expeditious analysis of phospholipid composition in human blood plasma by 31P NMR spectroscopy.Anal. Biochem. 1990; 185: 299-303Crossref PubMed Scopus (54) Google Scholar). In eukaryotes, the polyglycerophospholipid cardiolipin is synthesized and localized in the mitochondrion (13Schlame M. Ren M. Xu Y. Greenberg M.L. Haller I. Molecular symmetry in mitochondrial cardiolipins.Chem. Phys. Lipids. 2005; 138: 38-49Crossref PubMed Scopus (235) Google Scholar, 14Schlame M. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes.J. Lipid Res. 2008; 49: 1607-1620Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar) particularly the inner mitochondrial membrane (15Houtkooper R.H. Vaz F.M. Cardiolipin, the heart of mitochondrial metabolism.Cell. Mol. Life Sci. 2008; 65: 2493-2506Crossref PubMed Scopus (304) Google Scholar). As plasma is free of cells and subcellular organelles like mitochondria, cardiolipin was not detected. The limit of detection of plasma cardiolipin was found to be 4 nM using synthetic cardiolipin standards. Evidence for the existence of N-acylphosphatidylserine (N-acyl-PS) was first reported by Nelson in 1970 in sheep erythrocytes (16Nelson G.J. Studies on the lipids of sheep red blood cells. IV. The identification of a new phospholipid. N-acyl phosphatidyl serine.Biochem. Biophys. Res. Commun. 1970; 38: 261-265Crossref PubMed Scopus (20) Google Scholar). As part of the LIPID MAPS consortium's search for novel lipids, Guan et al. (17Guan Z. Li S. Smith D.C. Shaw W.A. Raetz C.R. Identification of N-acylphosphatidylserine molecules in eukaryotic cells.Biochemistry. 2007; 46: 14500-14513Crossref PubMed Scopus (39) Google Scholar) in 2007 reported the identification of a family of N-acyl-PS molecules present in mouse and pig brain, yeast, and mouse RAW264.7 macrophage tumor cells. The role of N-acyl-PS in animal cells was not investigated, but it was proposed that N-acyl-PS may function as a precursor of the bioactive signaling lipid N-acyl-L-serine (17Guan Z. Li S. Smith D.C. Shaw W.A. Raetz C.R. Identification of N-acylphosphatidylserine molecules in eukaryotic cells.Biochemistry. 2007; 46: 14500-14513Crossref PubMed Scopus (39) Google Scholar). Building on this work, we probed the human plasma SRM for the presence of the two most abundant ions of N-acyl-PS previously detected, i.e., 58:1 and 60:2, named for the number of carbons and double bonds each contains. Both ions containing a complex mixture of isobaric species were detected, with 58:1 making up 83% of the total N-acyl-PS detected (supplementary Table IIIB). We identified over 200 individual sphingolipids in the human plasma SRM. These results are summarized in Table 1 and levels of subspecies are shown in supplementary Table IV. Sphingomyelins (SM) accounted for the largest fraction of sphingolipids in plasma, and ∼100 subspecies were sufficiently abundant for their amounts to be estimated (supplementary Table IV). This number is about twice that of previous estimates of plasma SM subspecies (18Samuelsson B. Samuelsson L. Separation and identification of ceramides derived from human plasma sphingomyelins.J. Lipid Res. 1969; 10: 47-55Abstract Full Text PDF PubMed Google Scholar, 19Hirvisalo E.L. Renkonen O. Composition of human serum sphingomyelins.J. Lipid Res. 1970; 11: 54-59Abstract Full Text PDF PubMed Google Scholar, 20Kuksis A. Stachnyk O. Holub B.J. Improved quantitation of plasma lipids by direct gas-liquid chromatography.J. Lipid Res. 1969; 10: 660-667Abstract Full Text PDF PubMed Google Scholar, 21Vieu C. Terce F. Chevy F. Rolland C. Barbaras R. Chap H. Wolf C. Perret B. Collet X. Coupled assay of sphingomyelin and ceramide molecular species by gas liquid chromatography.J. Lipid Res. 2002; 43: 510-522Abstract Full Text Full Text PDF PubMed Google Scholar). Sphingosine was the most common sphingoid base, accounting for ∼61% of the total, followed by sphingadiene (18%) and sphinganine (9.5%); the remainder had other even- and odd-chain lengths, with the 16-carbon-chain length sphingosine accounting for ∼10%. The fatty acids of SM ranged in chain length from 13 to 28 carbons, of which over half were saturated (with 16:0 comprising about one-third of all SM subspecies), about 20% were monounsaturated (the most prevalent being 24:1), and there were small amounts of fatty acids with two (about 3%) and three (<1%) double bonds. Our approaches would not have detected 3-O-acyl-SM, which has been reported in trace amounts (22Kramer J.K. Blackwell B.A. Dugan M.E. Sauer F.D. Identification of a new sphingolipid 3-O-acyl-D-erythro-sphingomyelin in newborn pig and infant plasma.Biochim. Biophys. Acta. 1996; 1303: 47-55Crossref PubMed Scopus (7) Google Scholar), because the acyl-group would be hydrolyzed during extraction (23Shaner R.L. Allegood J.C. Park H. Wang E. Kelly S. Haynes C.A. Sullards M.C. Merrill Jr, A.H. Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers.J. Lipid Res. 2009; 50: 1692-1707Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar). These proportions are likely to vary among individuals because diet can affect the types and amounts of SM in plasma (24Nye W.H. Variability of plasma phospholipids in normal adults.Am. J. Clin. Nutr. 1969; 22: 5-7Crossref PubMed Google Scholar, 25Li Z. Basterr M.J. Hailemariam T.K. Hojjati M.R. Lu S. Liu J. Liu R. Zhou H. Jiang X.C. The effect of dietary sphingolipids on plasma sphingomyelin metabolism and atherosclerosis.Biochim. Biophys. Acta. 2005; 1735: 130-134Crossref PubMed Scopus (46) Google Scholar, 26Katsikas H. Wolf C. Blood sphingomyelins from two European countries.Biochim. Biophys. Acta. 1995; 1258: 95-100Crossref PubMed Scopus (12) Google Scholar). The majority of the ceramide monohexoses (CMHs) also had sphingosine as the most prevalent sphingoid base and fatty acid chain lengths ranging from 14 to 26 carbons, but fewer subspecies were quantified because the amounts were much lower than SM (∼1%). The major backbone subspecies were similar to SM except that the proportion of very-long-chain fatty acids is higher for CMH (supplementary Table IV). The CMH of human plasma was comprised of both glucosyl- (GlcCer) and galactosyl-ceramides (GalCer), as has been reported before (27Wells H.W. Jones M. Galactosylceramides in human plasma.Am. J. Clin. Pathol. 1973; 60: 890-896Crossref PubMed Scopus (5) Google Scholar, 28Vance D.E. Sweeley C.C. Quantitative determination of the neutral glycosyl ceramides in human blood.J. Lipid Res. 1967; 8: 621-630Abstract Full Text PDF PubMed Google Scholar, 29Koscielak J. Maslinski W. Zielenski J. Zdebska E. Brudzynski T. Miller-Podraza H. Cedergren B. Structures and fatty acid compositions of neutral glycosphingolipids of human plasma.Biochim. Biophys. Acta. 1978; 530: 385-393Crossref PubMed Scopus (13) Google Scholar), with higher proportions of GlcCer. More complex glycosphingolipids such as lactosylceramide were also detected but these were not quantified because the internal standards are not yet available. Plasma contained small amounts of free ceramide (4% of SM) with approximately the same spectrum of subspecies as were seen in SM and CMH, although many of the minor subspecies were present in amounts too low for quantitation (supplementary Table IV). A noteworthy feature of the free ceramides was that the fatty acid distribution differed substantially from that seen in SM or CMH with very little palmitic acid (∼5%) compared with the very-long-chain fatty acids (i.e., 24:0, ∼33%, and 24:1, ∼12%). A similar distinction has been reported in other analyses of human plasma (30Gorska M. Dobrzyn A. Zendzian-Piotrowska M. Namiot Z. Concentration and composition of free ceramides in human plasma.Horm. Metab. Res. 2002; 34: 466-468Crossref PubMed Scopus (13) Google Scholar, 31Ichi I. Nakahara K. Miyashita Y. Hidaka A. Kutsukake S. Inoue K. Maruyama T. Miwa Y. Harada-Shiba M. Tsushima M. et al.Association of ceramides in human plasma with risk factors of atherosclerosis.Lipids. 2006; 41: 859-863Crossref PubMed Scopus (77) Google Scholar). The N-acyl-derivatives of two novel categories of ceramides with 1-deoxy- and 1-(desoxymethyl)-sphingoid base backbones were also detected but not quantified (32Zitomer N.C. Mitchell T. Voss K.A. Bondy G.S. Pruett S.T. Garnier-Amblard E.C. Liebeskind L.S. Park H. Wang E. Sullards M.C. et al.Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals.J. Biol. Chem. 2009; 284: 4786-4795Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar). Free sphingoid bases were found in the human plasma SRM, with sphingosine 1-phosphate as the major species, followed by lower amounts of sphingosine, sphinganine, and sphinganine 1-phosphate. In addition to d18:1 sphingosine 1-phosphate (d indicates the presence of two hydroxyl groups, followed by the chain length and number of double bonds), there were smaller amounts of other chain lengths (d16:1 to d19:1). A similar profile has been seen in other studies (33Caligan T.B. Peters K. Ou J. Wang E. Saba J. Merrill Jr, A.H. A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples.Anal. Biochem. 2000; 281: 36-44Crossref PubMed Scopus (89) Google Scholar, 34Berdyshev E.V. Gorshkova I.A. Garcia J.G. Natarajan V. Hubbard W.C. Quantitative analysis of sphingoid base-1-phosphates as bisacetylated derivatives by liquid chromatography-tandem mass spectrometry.Anal. Biochem. 2005; 339: 129-136Crossref PubMed Scopus (112) Google Scholar, 35Jiang X. Han X. Characterization and direct quantitation of sphingoid base-1-phosphates from lipid extracts: a shotgun lipidomics approach.J. Lipid Res. 2006; 47: 1865-1873Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 36Scherer M. Schmitz G. Liebisch G. High-throughput analysis of sphingosine 1-phosphate, sphinganine 1-phosphate, and lysophosphatidic acid in plasma samples by liquid chromatography-tandem mass spectrometry.Clin. Chem. 2009; 55: 1218-1222Crossref PubMed Scopus (126) Google Scholar), although the amounts vary by several fold, which might be due to differences in diet, timing of collection, or storage of the sample. Sterols in plasma exist in both free and fatty-acyl esterified forms. For quantification of total (es

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Regulation of Lipolysis in Adipocytes

2007-06-25

Robin E. Duncan , Maryam Ahmadian , Kathy Jaworski +2 more

Lipolysis of white adipose tissue triacylglycerol stores results in the liberation of glycerol and nonesterified fatty acids that are released into the vasculature for use by other organs as energy … Lipolysis of white adipose tissue triacylglycerol stores results in the liberation of glycerol and nonesterified fatty acids that are released into the vasculature for use by other organs as energy substrates. In response to changes in nutritional state, lipolysis rates are precisely regulated through hormonal and biochemical signals. These signals modulate the activity of lipolytic enzymes and accessory proteins, allowing for maximal responsiveness of adipose tissue to changes in energy requirements and availability. Recently, a number of novel adipocyte triacylglyceride lipases have been identified, including desnutrin/ATGL, greatly expanding our understanding of adipocyte lipolysis. We have also begun to better appreciate the role of a number of nonenzymatic proteins that are critical to triacylglyceride breakdown. This review provides an overview of key mediators of lipolysis and the regulation of this process by changes in nutritional status and nutrient intakes.

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Acyl-Lipid Metabolism

2013-01-01

Yonghua Li‐Beisson , Basil S. Shorrosh , Fred Beisson +7 more

Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. … Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables.

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N<scp>UTRITIONAL</scp> R<scp>EGULATION OF</scp> M<scp>ILK</scp> F<scp>AT</scp> S<scp>YNTHESIS</scp>

2003-03-04

Dale E. Bauman , J.M. Griinari

Certain diets cause a marked reduction in milk fat production in ruminants. Commonly referred to as milk fat depression (MFD), the mechanism involves an interrelationship between rumen microbial processes and … Certain diets cause a marked reduction in milk fat production in ruminants. Commonly referred to as milk fat depression (MFD), the mechanism involves an interrelationship between rumen microbial processes and tissue metabolism. Numerous theories to explain this interrelationship have been proposed and investigations offer little support for theories that are based on a limitation in the supply of lipogenic precursors. Rather, the basis involves alterations in rumen biohydrogenation of dietary polyunsaturated fatty acids and a specific inhibition of mammary synthesis of milk fat. The biohydrogenation theory proposes that under certain dietary conditions, typical pathways of rumen biohydrogenation are altered to produce unique fatty acid intermediates that inhibit milk fat synthesis. Trans-10, cis-12 conjugated linoleic acid (CLA) has been identified as one example that is correlated with the reduction in milk fat. Investigations with pure isomers have shown that trans-10, cis-12 CLA is a potent inhibitor of milk fat synthesis, and similar to diet-induced MFD, the mechanism involves a coordinated reduction in mRNA abundance for key enzymes involved in the biochemical pathways of fat synthesis. A more complete identification of these naturally produced inhibitors of fat synthesis and delineation of cellular mechanisms may offer broader opportunities for application and understanding of the regulation of lipid metabolism.

Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production

1980-06-01

Julie McGarry , Daniel W. Foster

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth … The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More

The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux

2016-01-03

Varman T. Samuel , Gerald I. Shulman

Insulin resistance arises when the nutrient storage pathways evolved to maximize efficient energy utilization are exposed to chronic energy surplus. Ectopic lipid accumulation in liver and skeletal muscle triggers pathways … Insulin resistance arises when the nutrient storage pathways evolved to maximize efficient energy utilization are exposed to chronic energy surplus. Ectopic lipid accumulation in liver and skeletal muscle triggers pathways that impair insulin signaling, leading to reduced muscle glucose uptake and decreased hepatic glycogen synthesis. Muscle insulin resistance, due to ectopic lipid, precedes liver insulin resistance and diverts ingested glucose to the liver, resulting in increased hepatic de novo lipogenesis and hyperlipidemia. Subsequent macrophage infiltration into white adipose tissue (WAT) leads to increased lipolysis, which further increases hepatic triglyceride synthesis and hyperlipidemia due to increased fatty acid esterification. Macrophage-induced WAT lipolysis also stimulates hepatic gluconeogenesis, promoting fasting and postprandial hyperglycemia through increased fatty acid delivery to the liver, which results in increased hepatic acetyl-CoA content, a potent activator of pyruvate carboxylase, and increased glycerol conversion to glucose. These substrate-regulated processes are mostly independent of insulin signaling in the liver but are dependent on insulin signaling in WAT, which becomes defective with inflammation. Therapies that decrease ectopic lipid storage and diminish macrophage-induced WAT lipolysis will reverse the root causes of type 2 diabetes.

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The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease

2017-04-11

Jelske N. van der Veen , John P. Kennelly , Sereana Wan +3 more

Lipid droplets: a unified view of a dynamic organelle

2006-03-08

Sally Martin , Robert G. Parton

Dynamics and functions of lipid droplets

2018-12-06

James A. Olzmann , Pedro Carvalho

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Lipid biosynthesis.

1995-07-01

John B. Ohlrogge , John Browse

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Fucosylation-Mediated Suppression of Lipid Droplet Accumulation Induced by Low-Level L-Fucose Administration in 3T3-L1 Adipocytes

2025-06-24

Tomoya Nakamura , Tomohiko Nakao , Yuri Kominami +4 more | Kinases and Phosphatases

Obesity causes lifestyle-related diseases such as hypertension and type 2 diabetes and has become a global health concern. L-fucose (Fuc), a monosaccharide that can be derived from brown algae, has … Obesity causes lifestyle-related diseases such as hypertension and type 2 diabetes and has become a global health concern. L-fucose (Fuc), a monosaccharide that can be derived from brown algae, has been shown to strongly suppress lipid droplet accumulation in 3T3-L1 murine adipocytes at high concentrations via the activation of AMP-activated kinase (AMPK). Although low concentrations of Fuc also exhibited similar effects, the underlying mechanisms remain unclear. In this study, we investigated the effects of low-level Fuc on lipid metabolism, focusing on the role of fucosylation. Low-level Fuc did not induce AMPK phosphorylation but suppressed lipid droplet accumulation. This suppressive effect was abolished by co-treatment with the fucosylation inhibitor 2F-Peracetyl-Fucose (2F-PAF), suggesting that fucosylation plays a key role in the observed metabolic regulation. Furthermore, proteomic analysis combined with click chemistry pulldown suggested that proteins involved in the regulation of lipid metabolism, such as acetoacetyl-CoA synthetase enzymes and catalytic subunit alpha of cAMP-dependent protein kinase, are fucosylated or interact with fucose. These findings provide novel insights into the anti-obesity mechanisms of Fuc and highlight the physiological significance of protein fucosylation in adipocyte lipid metabolism.

Phase Separation and Biomolecular Condensate Formation Drives Plant Endomembrane and Autophagy Crosstalk

2025-06-24

Chiamaka Linda Mgbechidinma , Junfeng Cao , Liwen Jiang | Journal of Experimental Botany

Abstract Like other eukaryotes, plants are a rich hub of proteins, lipids, and nucleic acid biomolecules that undergo liquid-liquid phase separation to form liquid-like biomolecular condensates that facilitate diverse cellular … Abstract Like other eukaryotes, plants are a rich hub of proteins, lipids, and nucleic acid biomolecules that undergo liquid-liquid phase separation to form liquid-like biomolecular condensates that facilitate diverse cellular functions, especially upon biotic and abiotic stresses. Current plant-related research highlights the emerging role of biomolecular condensates in stress sensing, modulation, and response as an intricate mechanism for rapid and efficient stress adaptation. The cellular functions of condensates and their localization emphasize the importance of endomembrane systems in bridging the understanding of membrane-bound and membrane-less organelles and their compartmentalization. This review provides an overview of the recent updates and findings in plant phase separation and biomolecular condensate formation. With the increasing evidence of research pointing to a link between membrane-less condensates, autophagy, and the endomembrane system, we discuss the crosstalk between multivesicular body (MVB), autophagosome, and vacuole. We also elaborate on biomolecular condensates’ functional and regulatory roles in plant autophagosome formation at the early and late stages. Finally, we provide insights for future investigations on plant cellular biomolecular condensates as a means to pave the way for new frontiers of studies in improving agricultural plant yield, resilience, and other biotechnological applications.

Do α, α-(1-1)-Linked Disaccharides Enhance Stability of the Lipid Bilayer more than α, β-Linked Disaccharides under Desiccation?

2025-06-23

N. Shobha Rani , Archita Maiti , Snehasis Daschakraborty | The Journal of Physical Chemistry B

Disaccharides play a crucial role in protecting biological membranes from desiccation. Previous studies suggest that disaccharides with α,α-(1-1) glycosidic linkages, which adopt a clamshell conformation in the crystalline phase, are … Disaccharides play a crucial role in protecting biological membranes from desiccation. Previous studies suggest that disaccharides with α,α-(1-1) glycosidic linkages, which adopt a clamshell conformation in the crystalline phase, are more effective under dry conditions than those with α,β-glycosidic linkages, which have an open structure. However, their relative effectiveness under hydrated conditions remains unclear. To address this, we conducted molecular dynamics (MD) simulations of E. coli lipid membranes across hydration levels (h = 42 to 2) in the presence of α,α-galacto-trehalose and α,β-trehalose, comparing them with previously studied sucrose and α,α-trehalose. This selection allows us to evaluate the role of glycosidic linkages under varying hydration. Our results reveal that in the presence of even minimal water, all four disaccharides exhibit similar membrane-stabilizing effects, mitigating desiccation-induced stress by reducing lipid-lipid interactions and preventing excessive lipid packing. The structural advantage of α,α-(1-1)-linked sugars observed in the crystalline phase does not persist under hydrated conditions. These findings provide molecular-level insights into the protective mechanisms of disaccharides, suggesting that organisms may accumulate different sugars not necessarily for their intrinsic superiority but for availability and metabolic adaptability. This study refines our understanding of sugar-mediated membrane stabilization under desiccation stress, offering a broader perspective on the selection of protective solutes in biological systems.

Short coiled‐coil proteins from plants and metazoans – the ‘jacks of all trades’

2025-06-22

Agnieszka Sirko , Jarosław Poznański , Marzena Sieńko | FEBS Journal

The molecular functions of short coiled‐coil proteins remain poorly characterized. These proteins typically act as facilitators rather than essential components of metabolic processes, contributing to cellular homeostasis, and are aptly … The molecular functions of short coiled‐coil proteins remain poorly characterized. These proteins typically act as facilitators rather than essential components of metabolic processes, contributing to cellular homeostasis, and are aptly described as ‘jacks of all trades but masters of none’. They are found across diverse groups of organisms, including both plants and animals. LSU (RESPONSE TO LOW SULFUR) are plant proteins induced under sulfur deficiency and other environmental stresses. They participate in metabolic pathways, including sulfate assimilation, and manage oxidative stress by stabilizing and protecting antioxidative enzymes. In metazoans, SCOC (SHORT COILED‐COIL) proteins regulate autophagy initiation by recruiting proteins essential for forming autophagosomes—key vesicles involved in cellular degradation. SCOC proteins also interact with factors critical for maintaining membrane dynamics and intracellular transport. Despite some functional similarities, the roles of these proteins have diverged significantly between plants and animals, reflecting organism‐specific adaptations shaped by evolutionary pressures. This divergence underscores their adaptive versatility and highlights their potential as promising targets for future biological research.

Fatty acid compositions regulate BDE-153 migration in rice: Influence of biochar-derived organic matter and organic molecule

2025-06-20

Sai Wu , Weili Jia , Xinru Yang +4 more | Ecotoxicology and Environmental Safety

Gonadal Lipid Storage in Mytilus coruscus: A Comprehensive Gene Network and Key Gene Discovery

2025-06-19

Z. Y. Xin , Hao Wang , Bingqi Wei +5 more | Marine Biotechnology

Correction to “Evaluating the Oxidative Stability of Triacylglycerols in Rapeseed (Brassica napus) Oleosomes”

2025-06-19

| Journal of the American Oil Chemists Society

Sec14L6 Is a Phosphoinositide Transporter That Regulates Phosphoinositide Homeostasis and Biogenesis of Lipid Droplet

2025-06-18

Wei-Ke Ji , Tiantian Zhou , Xuewen Hu +2 more | Research Square (Research Square)

<title>Abstract</title> Lipid droplets (LDs) are evolutionarily conserved organelles crucial for cellular metabolism. Their biogenesis and growth occur in the endoplasmic reticulum (ER) and rely on lipid transfer between the ER … <title>Abstract</title> Lipid droplets (LDs) are evolutionarily conserved organelles crucial for cellular metabolism. Their biogenesis and growth occur in the endoplasmic reticulum (ER) and rely on lipid transfer between the ER and LDs. However, the molecular mechanisms remain poorly understood. In this study, we identified Sec14L6, a unique Sec14 protein family member, as a lipid transporter that regulates phosphoinositide homeostasis and biogenesis of LDs, and is required for the differentiation of adipose-derived mesenchymal stem cells. Sec14L6 directly binds to ACSL3, a known LD biogenesis factor, which facilitates the association of Sec14L6 with LD surface. Furthermore, we identify PGRMC1, an ER membrane protein, as an adaptor that recruits Sec14L6 to the ER, specifying a role for Sec14L6 at ER-LD interface. Targeted lipidomics revealed profound dysregulation of PIP homeostasis: residual LDs from Sec14L6-KO cells exhibited aberrant accumulation of PI4P and PI(4,5)P2, concomitant with a reduction of these PIPs within the ER compartment. In vitro assays demonstrate that Sec14L6 preferentially transports phosphoinositide-4-phosphate (PI4P) and PI(4,5)P2. Sec14L6 knockout (KO) severely impaired nascent LD formation, a defect rescued by wild-type Sec14L6 but not by lipid-transfer-deficient mutants. Our study identified Sec14L6 as a new factor that regulates PIP homeostasis and biogenesis of LDs via lipid transfer at ER-LD interface.

The transcription factor CeWRI3 functions in TAG accumulation through activating CeOLE2 in Cyperus esculentus

2025-06-18

Zhi Zou , Xiaowen Fu , Na Li +5 more | Plant Cell Reports

Gentian homologue of OIL BODY-ASSOCIATED PROTEIN1 is the key to a novel mechanism of growth recovery from cold stress via triacylglycerol hydrolysis.

2025-06-17

Hideyuki Takahashi , Hidetoshi Yamada , Motoki Shimizu +3 more | Plant Science

Comparative Analysis of the Expression of Genes Involved in Fatty Acid Synthesis Across Camelina Varieties

2025-06-17

Elisa Gómez , Gregorio Hueros , David Mostaza-Colado +3 more | Agriculture

Camelina sativa (L.) Crantz, a native European oilseed crop of the Brassicaceae family, is notable for its short life cycle, making it well-suited for crop rotation and diversification. Its seeds … Camelina sativa (L.) Crantz, a native European oilseed crop of the Brassicaceae family, is notable for its short life cycle, making it well-suited for crop rotation and diversification. Its seeds contain a high content of oil (36–47%) that is rich in polyunsaturated fatty acids (PUFAs) such as alpha-linolenic acid (ALA, C18:3, Ω-3) and linoleic acid (LA, C18:2, Ω-6). This oil has diverse industrial applications, including low-emission biofuels, animal feed, pharmaceuticals, biolubricants, bioplastics, and cosmetics. We analyzed the expression of seven key enzymes involved in fatty acid biosynthesis across nine C. sativa accessions at three stages of silique development using highly efficient qRT-PCR assays designed for the target genes and a normalizing control. Our detailed expression analysis revealed significant variation across varieties, with only the gene FAB2c exhibiting genotype-independent expression, indicating a constitutive and essential role in monounsaturated fatty acid (MUFA) biosynthesis. Other genes showed significant interactions between the variety and developmental stage, highlighting the combined influences of genetic background and silique maturation on gene regulation. V18 emerges as particularly promising, exhibiting elevated expression of genes linked to PUFA and VLCFA biosynthesis—traits of significance for food, biofuel, and industrial applications. These findings, together with the developed qRT-PCR assays, provide valuable tools for selecting Camelina varieties with optimized genetic profiles, highlighting the potential of harnessing natural transcriptional diversity for crop improvement.

Exploring Lipid Droplets for Enhancing Cytoskeletal Stability and Repair Capacity via Carbonized Polymer Dot-Assisted Fluorescence Imaging

2025-06-16

Zitong Yu , Shuping Xu | ACS Applied Bio Materials

Lipid droplets (LDs), as dynamic organelles, are regarded as core carriers of energy storage and participate in cell signaling and metabolic process regulation. The interaction between LDs and cytoskeletons may … Lipid droplets (LDs), as dynamic organelles, are regarded as core carriers of energy storage and participate in cell signaling and metabolic process regulation. The interaction between LDs and cytoskeletons may profoundly affect cell growth and pathological processes; however, direct evidence is absent. Our study employed an LD-targeted carbonized polymer dot (CPD) that exhibits high photostability and superior imaging capabilities with confocal fluorescence imaging to visually observe the behaviors of LDs in reinforcing cytoskeletons and assisting cytoskeletal repair. Results demonstrate that LDs could enhance the stability of the cytoskeletons, helping cells resist damage from external factors. Once they were damaged, the LDs could quickly increase in content to facilitate cytoskeletal repair. These findings reveal the important role of LDs as "regulatory hubs" and offer fresh perspectives on the mechanism behind LD-cytoskeleton interactions.

A Fluorescent Diaminoterephthalate Probe for Monitoring Lipid Droplet Dynamics and Ferroptosis in Mammalian Cells

2025-06-16

Shrishti P. Pandey , A. Kasem Chowdhury , Swagata Bhowmick +1 more | Chemistry - An Asian Journal

Abstract Ferroptosis is a Fe 2+ induced programmed cell death pathway that has attracted significant attention over the last decade. It is manifested in a marked increase in the polarity … Abstract Ferroptosis is a Fe 2+ induced programmed cell death pathway that has attracted significant attention over the last decade. It is manifested in a marked increase in the polarity of lipid droplets (LDs), as it involves lipid peroxidation. LD dynamics is affected significantly by this process. Design and choice of appropriate lipophilic fluorescent probes are crucial for monitoring these phenomena. This is the motivation for the present endeavor focused on R1, a cell permeable, lipophilic diaminoterephthalate fluorescent probe with a strongly polarity‐dependent fluorescence intensity and lifetime. Using confocal laser scanning microscopy (CLSM) and fluorescence lifetime imaging microscopy (FLIM), LD behavior in mammalian cells under ferroptosis‐inducing conditions has been observed. R1 has been found to exhibit a marked decrease in fluorescence intensity and lifetime in LDs upon treatment with erastin, thus reflecting the increased polarity brought about by ferroptosis. This sets the field for future use of R1 to investigate ferroptosis‐related processes, possibly leading to disease diagnostics and formulation of therapeutic strategies.

Structural and Functional Analysis of Plant Oil‐Body Lipase Eg<scp>LIP1</scp> From Elaeis guineensis

2025-06-16

Jia Rong Tey , Siti Fatimah , Maizom Hassan +2 more | Proteins Structure Function and Bioinformatics

EgLIP1 is an oil-body lipase (EC 3.1.1.3) overexpressed in the fruit mesocarp of Elaeis guineensis (oil palm). Despite its significant role in fruit ripening and the hydrolysis of of triacylglycerol … EgLIP1 is an oil-body lipase (EC 3.1.1.3) overexpressed in the fruit mesocarp of Elaeis guineensis (oil palm). Despite its significant role in fruit ripening and the hydrolysis of of triacylglycerol into free fatty acids (FFA) in oil palm, the molecular structure and functional understanding of EgLIP1 are yet to be fully elucidated. Phylogenetic analysis reveals that EgLIP1 shares homology with several plant oil-body lipases. The 3D structure of EgLIP1 was modeled using AlphaFold 2 with high confidence (pLDDT score of 89.7). Structural comparison with Rhizomucor miehei triacylglycerol lipase (RML) reveals that the regions β1, η1, α1, η2, β2, α2, α3, α4, α15, α16, and β15 represent novel insertions unique to EgLIP1, while the overall fold in other regions of the protein remains highly conserved in comparison to RML. Notably, an insertion of residue "PF" was also found in EgLIP1 and its plant orthologs. This insertion is located immediately before the lid domain helix, forming a kink facing toward the active lipase site. Enzyme-membrane surface interaction prediction suggests that α1, α3, α4, α15, and α16 are likely involved in anchoring EgLIP1 at the interface of the phospholipid monolayer of oil bodies. Molecular docking and molecular dynamics (MD) simulation analyses of EgLIP1 with its potential substrate, 1-palmitoylglycerol, demonstrate that the catalytic serine residue S308 and the GX oxyanion hole motif residue T223 can form hydrogen bonds with the carbonyl group of the ligand to initiate a nucleophilic attack on the substrate. Our structure-guided functional studies provide molecular insights into how EgLIP1 associates with oil bodies and catalyzes its potential substrates.

Clustering-based Method for Constructing the Phase Diagram of the Van Der Waals Model Fluid

2025-06-16

Pham Dinh Quoc Huy , Midhun Mohan Anila , Mateusz Chwastyk | Current Protein and Peptide Science

Introduction: Membraneless organelles, such as nucleoli, stress granules, and P-bodies, are not enclosed by lipid membranes; rather, they are formed through a process known as liquid-liquid phase separation. To fully … Introduction: Membraneless organelles, such as nucleoli, stress granules, and P-bodies, are not enclosed by lipid membranes; rather, they are formed through a process known as liquid-liquid phase separation. To fully understand the biophysics behind the formation and regulation of these organelles, knowledge that has significant implications for cellular biology and disease research, the creation of phase diagrams is essential. Phase diagrams help clarify the physical and chemical conditions under which these organelles form, exist, and function within cells. However, methods for creating phase diagrams are often limited when the equation of state is unknown, a challenge that becomes more pronounced with increasing system complexity. While several methods exist to address this issue, their application is not universal. Methods: We present a new method based on the SPACEBALL algorithm and cluster size monitoring, which enables the determination of binodal and spinodal line positions by analyzing system clustering during molecular dynamics simulations of a well-studied van der Waals fluid under various conditions. Results: Based on an analysis of the system’s clustering behavior, we constructed the phase diagram for the monoatomic van der Waals fluid simulated at various densities and temperatures, observing that uniformly distributed van der Waals beads aggregate, causing changes in the system’s density. Discussion: Using the generated data, we discuss how a fitting function can be used to determine the binodal line location, and how observations of the system’s density fluctuations can be used to determine the spinodal line location and assess the critical temperature. Conclusion: We have presented alternative methods for locating phase boundaries in protein solutions, where the absence of a validated equation of state necessitates innovative approaches and makes traditional methods challenging to apply. Our SPACEBALL-based approach enables the creation of phase diagrams using pure trajectories obtained from molecular dynamics simulations.

Lipid droplet accumulation in microglia and their potential roles

2025-06-14

Yunxia Li , Qi Zhao , Yan Wang +4 more | Lipids in Health and Disease

Microglia are the resident immune cells of the central nervous system (CNS), where lipid metabolism is critical for maintaining homeostasis. In response to various external stimuli, they demonstrate a range … Microglia are the resident immune cells of the central nervous system (CNS), where lipid metabolism is critical for maintaining homeostasis. In response to various external stimuli, they demonstrate a range of phenotypic expressions and lipid metabolic reprogramming. Lipid droplets (LDs) are dynamic organelles that function beyond energy storage, actively participating in neuropathological progress. Recent investigations have identified a subset of microglia characterized by the accumulation of LDs, referred to as "lipid-droplet-accumulating microglia" (LDAM). This review aims to investigate the processes involved in LD formation and degradation, the factors that modulate them, focusing particularly on the function of LDAM and their implications for CNS disorders. By synthesizing current evidence, we clarify the biological significance of LDs in these cells and their therapeutic targeting potential, providing new directions for future research.

Integrated transcriptomics and lipidomics reveal mechanisms regulating lipids formation and accumulation in oil body during walnut seed development

2025-06-14

Kaiyang Zhu , Yingying Zhang , Ji Ma +5 more | Planta

Hydroxy fatty acid analysis in seeds of Physaria and Paysonia species

2025-06-13

Jeum Kyu Hong , Mid‐Eum Park , Byeong-Cheol Oh +1 more | Genetic Resources and Crop Evolution

Lipid droplet dysmetabolism affects cell homeostasis in an in vitro model of Alzheimer disease

2025-06-13

Tânia Fernandes , Margarida Brito Caldeira , Tânia Melo +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Lipid droplets (LD) are dynamic organelles involved in neutral lipid storage, energy homeostasis, and can prevent lipotoxicity and oxidative distress. LD dysmetabolism has been considered a pathological hallmark in neurodegenerative … Lipid droplets (LD) are dynamic organelles involved in neutral lipid storage, energy homeostasis, and can prevent lipotoxicity and oxidative distress. LD dysmetabolism has been considered a pathological hallmark in neurodegenerative disorders, including Alzheimer disease (AD). In this study, we investigated the alterations in LD metabolism and their impact on mitochondria-associated membranes (MAM) in an in vitro model of AD, namely the mouse neuroblastoma cell (N2A) line overexpressing the amyloid precursor protein with the familial Swedish mutation (APPswe). In APPswe cells, we found depletion of LD associated with an accumulation of free fatty acids that can be related with the observed LD degradation by chaperone-mediated autophagy. In these cells we also found decreased levels of seipin, which might contribute to triacylglycerol accumulation. These lipid alterations are associated with increased levels of ROS and lipid peroxidation in APPswe cells. The pharmacological modulation of DGAT1, that mediates triacylglycerol synthesis, normalized LD size and improved ER-mitochondria contacts and mitochondrial function in APPswe cells. In summary, these observations suggest the involvement of altered LD metabolism in AD pathophysiology, which impact on MAM and mitochondria function leading to cell dyshomeostasis. Our findings also support the idea that LD are relevant therapeutic targets in AD.

Lipid Storage in Green Tissues Alters Redox Homeostasis, Malate Metabolism, Phospholipids, and Nitrogen Partitioning in Plants

2025-06-13

Somrutai Winichayakul , Hong Xue , Kim Richardson +3 more | Plant Physiology and Biochemistry

Diacylglycerol Acyltransferase1 Promotes Triacylglycerol Biosynthesis in Oil Tea (Camellia oleifera) Seeds through Transcriptional Activation by WRINKLED1

2025-06-12

Guang Zhao , Chancan Liao , Hongxu Long +2 more | Journal of Agricultural and Food Chemistry

Camellia oil, a nutritionally rich edible oil derived from Camellia oleifera seeds, is predominantly stored as triacylglycerol (TAG) during fruit maturation. However, a limited understanding of the genetic and regulatory … Camellia oil, a nutritionally rich edible oil derived from Camellia oleifera seeds, is predominantly stored as triacylglycerol (TAG) during fruit maturation. However, a limited understanding of the genetic and regulatory mechanisms governing Camellia oil accumulation has hindered efforts to optimize its yield. In this study, three C. oleifera diacylglycerol acyltransferase (CoDGAT) genes were identified and characterized, wherein CoDGAT1 emerged as the primary contributor to seed TAG biosynthesis, functioning within the endoplasmic reticulum and increasing seed oil content by 64.4% in transgenic plant. Through weighted gene coexpression network analysis, we identified WRINKLED1 (CoWRI1) as a candidate transcriptional regulator of CoDGAT1. Both genes exhibited significant upregulation during seed maturation. Mechanistically, CoWRI1 activated CoDGAT1 by directly binding to AW-box motifs in its promoter, thereby promoting TAG accumulation. Additionally, CoWRI1 expression was suppressed by salicylic acid, methyl jasmonate, and darkness, suggesting that phytohormones and environmental signals modulate TAG accumulation through the WRI1-DGAT1 pathway. These findings provide an important basis for improving Camellia oil production through biotechnological manipulation of DGAT1 and WRI1 genes.

Multicolor Microscopic In Vivo Imaging of the Formation and Disappearance of Lipid Droplets Using BODIPY-Based Red and Deep-Red Fluorescent Probes

2025-06-12

Mayuko Shimanuki , Risa Uda , Shuichi Shiozaki +1 more | ACS Applied Bio Materials

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. As the number and size of lipid droplets (LDs) generally increase in hepatocytes during the early stages … Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. As the number and size of lipid droplets (LDs) generally increase in hepatocytes during the early stages of NAFLD, visualization of LDs in living samples is of great importance for properly diagnosing and treating NAFLD. Here, red and deep-red fluorescent probes (BPMP-2Thia and BPMP-4Thia) based on boron-dipyrromethene (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, BODIPY) are developed for the visualization of LDs in the liver of normal and NAFLD model mice as well as cultured cells. BPMP-2Thia and BPMP-4Thia exhibit bright emission in low-polarity solvents, which simulate the microenvironment of LDs, and they exhibit high selectivity for LDs, costaining capability, good biocompatibility, and high photostability in living cells and mice. Multicolor confocal microscopy combined with intravenous administration of an LD-specific probe, vascular endothelial marker, and nucleus-specific probe in mice enables the quantitative visualization of LD growth, including visualization of the disordered sinusoidal network and flattened hepatocyte nuclei. Furthermore, this simultaneous imaging method allows evaluation of the reduction in the number and size of LDs in the hepatic tissues of fatty liver model mice upon shifting from a high-fat to normal diet.

The interplay between lipid droplets and Parkinson's disease

2025-06-12

Xinru Zhao , Yingying Gu , Jiayi Wang +5 more | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Astrocyte Lipid Droplet Dynamics Orchestrate Neurological Disorders and Therapeutic Horizons

2025-06-08

Jiani Zhong , Yanyi Peng , Lingyue Zhang +2 more | Small Science

Astrocytes, the predominant glial cells in the central nervous system (CNS), play a pivotal role in maintaining neuronal homeostasis and function. Accumulating evidence suggests that astrocytic dysfunction is closely associated … Astrocytes, the predominant glial cells in the central nervous system (CNS), play a pivotal role in maintaining neuronal homeostasis and function. Accumulating evidence suggests that astrocytic dysfunction is closely associated with the pathogenesis of various neurological disorders, including neurodegenerative diseases, ischemic stroke (IS), epilepsy, and glioma. Lipid droplets (LDs), ubiquitous intracellular lipid storage organelles, exhibit metabolic abnormalities that are commonly observed in these neurological conditions, particularly in astrocytes, where LD metabolic dysregulation may serve as a critical link between glial dysfunction and neuronal damage. However, a systematic understanding of the regulatory mechanisms governing LD metabolism in astrocytes and their relationship to the pathogenesis of neurological diseases remains elusive. This article reviews the biology and pathology of astrocytes and summarizes the characteristics, regulatory factors, and abnormalities of LD metabolism in astrocytes, highlighting its association with neurodegenerative diseases, stroke, epilepsy, and glioma. Finally, we propose future research directions, emphasizing the need for integrative multiomics approaches and innovative regulatory technologies to elucidate the role of astrocytic LD metabolism in neurological disorders. Understanding the dysregulation of LD metabolism in astrocytes may provide novel insights into disease etiology and facilitate the development of glial‐targeted diagnostic and therapeutic strategies.

The balancing act between lipid droplets and lysosomes for membrane functionality in age-related neurodegeneration and inflammation

2025-06-06

Tsap Mariana , Halyna R. Shcherbata | Progress in Lipid Research

WRINKLED1 transcription factor activates lipid biosynthesis to enhance oil accumulation in Pinus koraiensis

2025-06-03

Yuxin Song , Zeyu An , He Zhang +7 more | Plant Physiology and Biochemistry

Toward sustainable crops: integrating vegetative (non-seed) lipid storage, carbon-nitrogen dynamics, and redox regulation

2025-06-03

Somrutai Winichayakul , Nick Roberts | Frontiers in Plant Science

The global challenges of climate change and rising energy demands necessitate innovative agricultural solutions. One promising strategy is the transformation of photosynthetic tissues into lipid-rich organs, providing energy-dense biomass for … The global challenges of climate change and rising energy demands necessitate innovative agricultural solutions. One promising strategy is the transformation of photosynthetic tissues into lipid-rich organs, providing energy-dense biomass for biofuel production while enhancing carbon sequestration. However, these metabolic shifts require substantial NADPH and ATP, reshaping cellular processes such as the Calvin-Benson cycle, glycolysis, and oxidative pentose phosphate pathways. This review explores the intricate metabolic and regulatory networks underpinning lipid accumulation, with a focus on carbon/nitrogen partitioning, redox regulation, and their implications for plant stress tolerance and productivity. Furthermore, we highlight recent progress in field applications, multi-omics integration, and emerging strategies to optimize lipid accumulation in crops while mitigating trade-offs in biomass yield and agronomic performance. Understanding these complex interactions will be essential for developing sustainable, high-lipid crops that support bioenergy production and climate-resilient agriculture.

Optogenetic perturbation of lipid droplet localization affects lipid metabolism and development in Drosophila

2025-06-01

Xin Deng , Wei Wang , Dandan Peng +5 more | Journal of Lipid Research

Lipid droplets (LDs) are dynamic organelles crucial for lipid storage and homeostasis. Despite extensive documentation of their importance, the causal relationship between LD localization and function in health and disease … Lipid droplets (LDs) are dynamic organelles crucial for lipid storage and homeostasis. Despite extensive documentation of their importance, the causal relationship between LD localization and function in health and disease remains inadequately understood. Here, we developed optogenetics-based tools, termed 'Opto-LDs', which facilitate the interaction between LDs and motor proteins in a light-dependent manner, enabling precise control of LD localization within cells. Utilizing these optogenetic modules, we demonstrated that light-induced relocation of LDs to the periphery of hepatocytes results in elevated very-low-density lipoprotein (VLDL) secretion, recapturing the beneficial effect of insulin in vitro. Furthermore, our studies in transgenic Drosophila revealed that proper LD localization is critical for embryonic development, with mistargeting of LDs significantly affecting egg hatching success. In summary, our work underscores the great importance of LD localization in lipid metabolism and development, and our developed tools offer valuable insights into the functions of LDs in health and disease.

NRF2 regulates lipid droplet dynamics to prevent lipotoxicity

2025-06-01

Christopher T. Prevost , William B. Gansereit , David F. Kashatus | iScience

Perilipin 2 mediates progression of lung adenocarcinoma by modulating lipid metabolism

2025-06-01

Kana Miyata‐Morita , Akira Kawashima , Mitsuo Kiriya +6 more | American Journal Of Pathology