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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi

4 Issues per year

CiteScore 2017: 2.48

SCImago Journal Rank (SJR) 2017: 1.021
Source Normalized Impact per Paper (SNIP) 2017: 0.830

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Volume 26, Issue 1


Intramyocellular fat storage in metabolic diseases

Claire Laurens
  • INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France
  • University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Cedric Moro
  • Corresponding author
  • INSERM, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France
  • University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-12-19 | DOI: https://doi.org/10.1515/hmbci-2015-0045


Over the past decades, obesity and its metabolic co-morbidities such as type 2 diabetes (T2D) developed to reach an endemic scale. However, the mechanisms leading to the development of T2D are still poorly understood. One main predictor for T2D seems to be lipid accumulation in “non-adipose” tissues, best known as ectopic lipid storage. A growing body of data suggests that these lipids may play a role in impairing insulin action in metabolic tissues, such as liver and skeletal muscle. This review aims to discuss recent literature linking ectopic lipid storage and insulin resistance, with emphasis on lipid deposition in skeletal muscle. The link between skeletal muscle lipid content and insulin sensitivity, as well as the mechanisms of lipid-induced insulin resistance and potential therapeutic strategies to alleviate lipotoxic lipid pressure in skeletal muscle will be discussed.

Keywords: ectopic lipids; IMTG; lipotoxicity; skeletal muscle; type 2 diabetes


  • 1.

    Kissebah AH, Krakower GR. Regional adiposity and morbidity. Physiol Rev 1994;74:761–811.Google Scholar

  • 2.

    Defronzo RA, Simonson D, Ferrannini E, Barrett E. Insulin resistance: a universal finding in diabetic states. Bull Schweiz Akad Med Wiss 1981:223–38.Google Scholar

  • 3.

    DeFronzo RA, Hendler R, Simonson D. Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes 1982;31:795–801.CrossrefGoogle Scholar

  • 4.

    Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell 2012;148:852–71.Google Scholar

  • 5.

    Samocha-Bonet D, Dixit VD, Kahn CR, Leibel RL, Lin X, Nieuwdorp M, Pietilainen KH, Rabasa-Lhoret R, Roden M, Scherer PE, Klein S, Ravussin E. Metabolically healthy and unhealthy obese–the 2013 Stock Conference report. Obes Rev 2014;15:697–708.Google Scholar

  • 6.

    El-Assaad W, Buteau J, Peyot ML, Nolan C, Roduit R, Hardy S, Joly E, Dbaibo G, Rosenberg L, Prentki M. Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology 2003;144:4154–63.CrossrefGoogle Scholar

  • 7.

    Krssak M, Brehm A, Bernroider E, Anderwald C, Nowotny P, Dalla Man C, Cobelli C, Cline GW, Shulman GI, Waldhausl W, Roden M. Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes 2004;53:3048–56.CrossrefGoogle Scholar

  • 8.

    Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005;54:603–8.CrossrefGoogle Scholar

  • 9.

    Coen PM, Hames KC, Leachman EM, DeLany JP, Ritov VB, Menshikova EV, Dube JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity (Silver Spring) 2013;21:2362–71.CrossrefGoogle Scholar

  • 10.

    Moro C, Galgani JE, Luu L, Pasarica M, Mairal A, Bajpeyi S, Schmitz G, Langin D, Liebisch G, Smith SR. Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals. J Clin Endocrinol Metab 2009;94:3440–7.CrossrefGoogle Scholar

  • 11.

    Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Testolin G, Pozza G, Del Maschio A, Luzi L. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H–13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 1999;48:1600–6.CrossrefGoogle Scholar

  • 12.

    Coen PM, Dube JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FG, Goodpaster BH. Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 2010;59:80–8.Google Scholar

  • 13.

    Virkamaki A, Korsheninnikova E, Seppala-Lindroos A, Vehkavaara S, Goto T, Halavaara J, Hakkinen AM, Yki-Jarvinen H. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes 2001;50:2337–43.CrossrefGoogle Scholar

  • 14.

    DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009;32 Suppl 2:S157–63.CrossrefGoogle Scholar

  • 15.

    Ferrannini E, Simonson DC, Katz LD, Reichard G, Jr., Bevilacqua S, Barrett EJ, Olsson M, DeFronzo RA. The disposal of an oral glucose load in patients with non-insulin-dependent diabetes. Metabolism 1988;37:79–85.Google Scholar

  • 16.

    Vettor R, Milan G, Franzin C, Sanna M, De Coppi P, Rizzuto R, Federspil G. The origin of intermuscular adipose tissue and its pathophysiological implications. Am J Physiol Endocrinol Metab 2009;297:E987–98.Google Scholar

  • 17.

    Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes 2011;60:2588–97.CrossrefGoogle Scholar

  • 18.

    Goodpaster BH, Thaete FL, Kelley DE. Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 2000;71:885–92.Google Scholar

  • 19.

    Yim JE, Heshka S, Albu J, Heymsfield S, Kuznia P, Harris T, Gallagher D. Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk. Int J Obes (Lond) 2007;31:1400–5.CrossrefGoogle Scholar

  • 20.

    Boettcher M, Machann J, Stefan N, Thamer C, Haring HU, Claussen CD, Fritsche A, Schick F. Intermuscular adipose tissue (IMAT): association with other adipose tissue compartments and insulin sensitivity. J Magn Reson Imaging 2009;29:1340–5.CrossrefGoogle Scholar

  • 21.

    Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, Schwartz AV, Kritchevsky S, Newman AB. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 2003;26:372–9.CrossrefGoogle Scholar

  • 22.

    Arrighi N, Moratal C, Clement N, Giorgetti-Peraldi S, Peraldi P, Loubat A, Kurzenne JY, Dani C, Chopard A, Dechesne CA. Characterization of adipocytes derived from fibro/adipogenic progenitors resident in human skeletal muscle. Cell Death Dis 2015;6:e1733.CrossrefGoogle Scholar

  • 23.

    van Loon LJ. Use of intramuscular triacylglycerol as a substrate source during exercise in humans. J Appl Physiol (1985) 2004;97:1170–87.Google Scholar

  • 24.

    Kiens B. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 2006;86:205–43.CrossrefGoogle Scholar

  • 25.

    Dagenais GR, Tancredi RG, Zierler KL. Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest 1976;58:421–31.CrossrefGoogle Scholar

  • 26.

    Kanaley JA, Shadid S, Sheehan MT, Guo Z, Jensen MD. Relationship between plasma free fatty acid, intramyocellular triglycerides and long-chain acylcarnitines in resting humans. J Physiol 2009;587:5939–50.Google Scholar

  • 27.

    Guo Z, Burguera B, Jensen MD. Kinetics of intramuscular triglyceride fatty acids in exercising humans. J Appl Physiol (1985) 2000;89:2057–64.Google Scholar

  • 28.

    Roepstorff C, Steffensen CH, Madsen M, Stallknecht B, Kanstrup IL, Richter EA, Kiens B. Gender differences in substrate utilization during submaximal exercise in endurance-trained subjects. Am J Physiol Endocrinol Metab 2002;282:E435–47.Google Scholar

  • 29.

    Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999;42:113–6.Google Scholar

  • 30.

    McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002;51:7–18.CrossrefGoogle Scholar

  • 31.

    Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 2001;86:5755–61.CrossrefGoogle Scholar

  • 32.

    Tarnopolsky MA, Rennie CD, Robertshaw HA, Fedak-Tarnopolsky SN, Devries MC, Hamadeh MJ. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul Integr Comp Physiol 2007;292:R1271–78.Google Scholar

  • 33.

    Jansson E, Kaijser L. Substrate utilization and enzymes in skeletal muscle of extremely endurance-trained men. J Appl Physiol (1985) 1987;62:999–1005.Google Scholar

  • 34.

    Jong-Yeon K, Hickner RC, Dohm GL, Houmard JA. Long- and medium-chain fatty acid oxidation is increased in exercise-trained human skeletal muscle. Metabolism 2002;51:460–4.CrossrefGoogle Scholar

  • 35.

    Moro C, Bajpeyi S, Smith SR. Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity. Am J Physiol Endocrinol Metab 2008;294:E203–13.Google Scholar

  • 36.

    Sacchetti M, Saltin B, Olsen DB, van Hall G. High triacylglycerol turnover rate in human skeletal muscle. J Physiol 2004;561:883–91.Google Scholar

  • 37.

    van Loon LJ, Goodpaster BH. Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state. Pflugers Arch 2006;451:606–16.Google Scholar

  • 38.

    van Loon LJ, Koopman R, Manders R, van der Weegen W, van Kranenburg GP, Keizer HA. Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes. Am J Physiol Endocrinol Metab 2004;287:E558–65.Google Scholar

  • 39.

    Badin PM, Loubiere C, Coonen M, Louche K, Tavernier G, Bourlier V, Mairal A, Rustan AC, Smith SR, Langin D, Moro C. Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58. J Lipid Res 2012;53:839–48.CrossrefGoogle Scholar

  • 40.

    Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002;277:50230–6.Google Scholar

  • 41.

    Fillmore N, Keung W, Kelly SE, Proctor SD, Lopaschuk GD, Ussher JR. Accumulation of ceramide in slow-twitch muscle contributes to the development of insulin resistance in the obese JCR:LA-cp rat. Exp Physiol 2015;100:730–41.CrossrefGoogle Scholar

  • 42.

    Holloway GP, Han XX, Jain SS, Bonen A, Chabowski A. Chronic muscle stimulation improves insulin sensitivity while increasing subcellular lipid droplets and reducing selected diacylglycerol and ceramide species in obese Zucker rats. Diabetologia 2014;57:832–40.CrossrefGoogle Scholar

  • 43.

    Szendroedi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, Jelenik T, Muller J, Herder C, Nowotny P, Shulman GI, Roden M. Role of diacylglycerol activation of PKCtheta in lipid-induced muscle insulin resistance in humans. Proc Natl Acad Sci USA 2014;111:9597–602.Google Scholar

  • 44.

    Straczkowski M, Kowalska I, Nikolajuk A, Dzienis-Straczkowska S, Kinalska I, Baranowski M, Zendzian-Piotrowska M, Brzezinska Z, Gorski J. Relationship between insulin sensitivity and sphingomyelin signaling pathway in human skeletal muscle. Diabetes 2004;53:1215–21.CrossrefGoogle Scholar

  • 45.

    Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia 2011;54:1147–56.CrossrefGoogle Scholar

  • 46.

    Helge JW, Dobrzyn A, Saltin B, Gorski J. Exercise and training effects on ceramide metabolism in human skeletal muscle. Exp Physiol 2004;89:119–27.Google Scholar

  • 47.

    Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002;51:2005–11.CrossrefGoogle Scholar

  • 48.

    Lessard SJ, Lo Giudice SL, Lau W, Reid JJ, Turner N, Febbraio MA, Hawley JA, Watt MJ. Rosiglitazone enhances glucose tolerance by mechanisms other than reduction of fatty acid accumulation within skeletal muscle. Endocrinology 2004;145:5665–70.Google Scholar

  • 49.

    Timmers S, Nabben M, Bosma M, van Bree B, Lenaers E, van Beurden D, Schaart G, Westerterp-Plantenga MS, Langhans W, Hesselink MK, Schrauwen-Hinderling VB, Schrauwen P. Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity. Proc Natl Acad Sci USA 2012;109:11711–6.Google Scholar

  • 50.

    Bergman BC, Hunerdosse DM, Kerege A, Playdon MC, Perreault L. Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans. Diabetologia 2012;55:1140–50.CrossrefGoogle Scholar

  • 51.

    Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 1999;103:253–9.Google Scholar

  • 52.

    Li Y, Soos TJ, Li X, Wu J, Degennaro M, Sun X, Littman DR, Birnbaum MJ, Polakiewicz RD. Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101). J Biol Chem 2004;279:45304–7.Google Scholar

  • 53.

    Badin PM, Vila IK, Louche K, Mairal A, Marques MA, Bourlier V, Tavernier G, Langin D, Moro C. High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle. Endocrinology 2013;154:1444–53.Google Scholar

  • 54.

    Ussher JR, Koves TR, Cadete VJ, Zhang L, Jaswal JS, Swyrd SJ, Lopaschuk DG, Proctor SD, Keung W, Muoio DM, Lopaschuk GD. Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption. Diabetes 2010;59:2453–64.CrossrefGoogle Scholar

  • 55.

    Holland WL, Knotts TA, Chavez JA, Wang LP, Hoehn KL, Summers SA. Lipid mediators of insulin resistance. Nutr Rev 2007;65:S39–46.CrossrefGoogle Scholar

  • 56.

    Bikman BT, Summers SA. Ceramides as modulators of cellular and whole-body metabolism. J Clin Invest 2011;121:4222–30.Google Scholar

  • 57.

    Powell DJ, Turban S, Gray A, Hajduch E, Hundal HS. Intracellular ceramide synthesis and protein kinase Czeta activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem J 2004;382:619–29.Google Scholar

  • 58.

    Goudriaan JR, Dahlmans VE, Teusink B, Ouwens DM, Febbraio M, Maassen JA, Romijn JA, Havekes LM, Voshol PJ. CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice. J Lipid Res 2003;44:2270–7.CrossrefGoogle Scholar

  • 59.

    Hajri T, Han XX, Bonen A, Abumrad NA. Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice. J Clin Invest 2002;109:1381–9.Google Scholar

  • 60.

    Kim JK, Gimeno RE, Higashimori T, Kim HJ, Choi H, Punreddy S, Mozell RL, Tan G, Stricker-Krongrad A, Hirsch DJ, Fillmore JJ, Liu ZX, Dong J, Cline G, Stahl A, Lodish HF, Shulman GI. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle. J Clin Invest 2004;113:756–63.Google Scholar

  • 61.

    Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH. Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest 2007;117:1679–89.CrossrefGoogle Scholar

  • 62.

    Levin MC, Monetti M, Watt MJ, Sajan MP, Stevens RD, Bain JR, Newgard CB, Farese RV, Sr., Farese RV, Jr. Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle. Am J Physiol Endocrinol Metab 2007;293:E1772–81.Google Scholar

  • 63.

    Timmers S, de Vogel-van den Bosch J, Hesselink MK, van Beurden D, Schaart G, Ferraz MJ, Losen M, Martinez-Martinez P, De Baets MH, Aerts JM, Schrauwen P. Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. PLoS One 2011;6:e14503.CrossrefGoogle Scholar

  • 64.

    Sparks LM, Bosma M, Brouwers B, van de Weijer T, Bilet L, Schaart G, Moonen-Kornips E, Eichmann TO, Lass A, Hesselink MK, Schrauwen P. Reduced incorporation of fatty acids into triacylglycerol in myotubes from obese individuals with type 2 diabetes. Diabetes 2014;63:1583–93.CrossrefGoogle Scholar

  • 65.

    Olofsson SO, Bostrom P, Andersson L, Rutberg M, Perman J, Boren J. Lipid droplets as dynamic organelles connecting storage and efflux of lipids. Biochim Biophys Acta 2009;1791:448–58.Google Scholar

  • 66.

    Fujimoto T, Ohsaki Y. Cytoplasmic lipid droplets: rediscovery of an old structure as a unique platform. Ann NY Acad Sci 2006;1086:104–15.Google Scholar

  • 67.

    Tauchi-Sato K, Ozeki S, Houjou T, Taguchi R, Fujimoto T. The surface of lipid droplets is a phospholipid monolayer with a unique Fatty Acid composition. J Biol Chem 2002;277:44507–12.Google Scholar

  • 68.

    Gjelstad IM, Haugen F, Gulseth HL, Norheim F, Jans A, Bakke SS, Raastad T, Tjonna AE, Wisloff U, Blaak EE, Riserus U, Gaster M, Roche HM, Birkeland KI, Drevon CA. Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance. Arch Physiol Biochem 2012;118:22–30.CrossrefGoogle Scholar

  • 69.

    Mason RR, Mokhtar R, Matzaris M, Selathurai A, Kowalski GM, Mokbel N, Meikle PJ, Bruce CR, Watt MJ. PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle. Mol Metab 2014;3:652–63.CrossrefGoogle Scholar

  • 70.

    Granneman JG, Moore HP, Krishnamoorthy R, Rathod M. Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). J Biol Chem 2009;284:34538–44.Google Scholar

  • 71.

    Granneman JG, Moore HP, Granneman RL, Greenberg AS, Obin MS, Zhu Z. Analysis of lipolytic protein trafficking and interactions in adipocytes. J Biol Chem 2007;282:5726–35.Google Scholar

  • 72.

    Subramanian V, Rothenberg A, Gomez C, Cohen AW, Garcia A, Bhattacharyya S, Shapiro L, Dolios G, Wang R, Lisanti MP, Brasaemle DL. Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes. J Biol Chem 2004;279:42062–71.Google Scholar

  • 73.

    Wang H, Sztalryd C. Oxidative tissue: perilipin 5 links storage with the furnace. Trends Endocrinol Metab 2011;22:197–203.CrossrefGoogle Scholar

  • 74.

    Wang H, Sreenivasan U, Hu H, Saladino A, Polster BM, Lund LM, Gong DW, Stanley WC, Sztalryd C. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J Lipid Res 2011;52:2159–68.CrossrefGoogle Scholar

  • 75.

    Bosma M, Minnaard R, Sparks LM, Schaart G, Losen M, de Baets MH, Duimel H, Kersten S, Bickel PE, Schrauwen P, Hesselink MK. The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria. Histochem Cell Biol 2012;137:205–16.Google Scholar

  • 76.

    Lass A, Zimmermann R, Oberer M, Zechner R. Lipolysis – a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog Lipid Res 2011;50:14–27.CrossrefGoogle Scholar

  • 77.

    Tornqvist H, Belfrage P. Purification and some properties of a monoacylglycerol-hydrolyzing enzyme of rat adipose tissue. J Biol Chem 1976;251:813–9.Google Scholar

  • 78.

    Karlsson M, Contreras JA, Hellman U, Tornqvist H, Holm C. cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases. J Biol Chem 1997;272:27218–23.Google Scholar

  • 79.

    Taschler U, Radner FP, Heier C, Schreiber R, Schweiger M, Schoiswohl G, Preiss-Landl K, Jaeger D, Reiter B, Koefeler HC, Wojciechowski J, Theussl C, Penninger JM, Lass A, Haemmerle G, Zechner R, Zimmermann R. Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J Biol Chem 2011;286:17467–77.Google Scholar

  • 80.

    Zhao S, Mugabo Y, Iglesias J, Xie L, Delghingaro-Augusto V, Lussier R, Peyot ML, Joly E, Taib B, Davis MA, Brown JM, Abousalham A, Gaisano H, Madiraju SR, Prentki M. alpha/beta-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion. Cell Metab 2014;19: 993–1007.CrossrefGoogle Scholar

  • 81.

    Badin PM, Louche K, Mairal A, Liebisch G, Schmitz G, Rustan AC, Smith SR, Langin D, Moro C. Altered skeletal muscle lipase expression and activity contribute to insulin resistance in humans. Diabetes 2011;60:1734–42.CrossrefGoogle Scholar

  • 82.

    Jocken JW, Moro C, Goossens GH, Hansen D, Mairal A, Hesselink MK, Langin D, van Loon LJ, Blaak EE. Skeletal muscle lipase content and activity in obesity and type 2 diabetes. J Clin Endocrinol Metab 2010;95:5449–53.CrossrefGoogle Scholar

  • 83.

    Kase ET, Feng YZ, Badin PM, Bakke SS, Laurens C, Coue M, Langin D, Gaster M, Thoresen GH, Rustan AC, Moro C. Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals. Biochim Biophys Acta 2015;1851:1194–201.Google Scholar

  • 84.

    Vaughan M, Berger JE, Steinberg D. Hormone-sensitive lipase and monoglyceride lipase activities in adipose tissue. J Biol Chem 1964;239:401–9.Google Scholar

  • 85.

    Prats C, Donsmark M, Qvortrup K, Londos C, Sztalryd C, Holm C, Galbo H, Ploug T. Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J Lipid Res 2006;47:2392–9.CrossrefGoogle Scholar

  • 86.

    Haemmerle G, Zimmermann R, Hayn M, Theussl C, Waeg G, Wagner E, Sattler W, Magin TM, Wagner EF, Zechner R. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 2002;277:4806–15.Google Scholar

  • 87.

    Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004;306:1383–6.Google Scholar

  • 88.

    Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006;312:734–7.Google Scholar

  • 89.

    Fischer J, Lefevre C, Morava E, Mussini JM, Laforet P, Negre-Salvayre A, Lathrop M, Salvayre R. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet 2007;39:28–30.CrossrefGoogle Scholar

  • 90.

    Sitnick MT, Basantani MK, Cai L, Schoiswohl G, Yazbeck CF, Distefano G, Ritov V, DeLany JP, Schreiber R, Stolz DB, Gardner NP, Kienesberger PC, Pulinilkunnil T, Zechner R, Goodpaster BH, Coen P, Kershaw EE. Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes 2013;62:3350–61.CrossrefGoogle Scholar

  • 91.

    Dube JJ, Sitnick MT, Schoiswohl G, Wills RC, Basantani MK, Cai L, Pulinilkunnil T, Kershaw EE. Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice. Am J Physiol Endocrinol Metab 2015;308:E879–90.Google Scholar

  • 92.

    Hoy AJ, Bruce CR, Turpin SM, Morris AJ, Febbraio MA, Watt MJ. Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation. Endocrinology 2011;152:48–58.Google Scholar

  • 93.

    Lefevre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R, Lakhdar H, Wollenberg A, Verret JL, Weissenbach J, Ozguc M, Lathrop M, Prud’homme JF, Fischer J. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/ thioesterase subfamily, in Chanarin-Dorfman syndrome. Am J Hum Genet 2001;69:1002–12.CrossrefGoogle Scholar

  • 94.

    Yang X, Lu X, Lombes M, Rha GB, Chi YI, Guerin TM, Smart EJ, Liu J. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab 2010;11:194–205.Google Scholar

  • 95.

    Schweiger M, Paar M, Eder C, Brandis J, Moser E, Gorkiewicz G, Grond S, Radner FP, Cerk I, Cornaciu I, Oberer M, Kersten S, Zechner R, Zimmermann R, Lass A. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase. J Lipid Res 2012;53:2307–17.Google Scholar

  • 96.

    Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol 2013;27:73–83.CrossrefGoogle Scholar

  • 97.

    Holland WL, Bikman BT, Wang LP, Yuguang G, Sargent KM, Bulchand S, Knotts TA, Shui G, Clegg DJ, Wenk MR, Pagliassotti MJ, Scherer PE, Summers SA. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest 2011;121:1858–70.Google Scholar

  • 98.

    Hotamisligil GS. Inflammation and endoplasmic reticulum stress in obesity and diabetes. Int J Obes (Lond) 2008;32 Suppl 7:S52–4.CrossrefGoogle Scholar

  • 99.

    Turpin SM, Lancaster GI, Darby I, Febbraio MA, Watt MJ. Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab 2006;291:E1341–50.Google Scholar

About the article

Corresponding author: Cedric Moro, Ph.D., INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires, CHU Rangueil, BP 84225, 1 Avenue Jean Poulhès, 31432 Toulouse Cedex 4, France, Phone: +33(0)561325626, Fax: +33(0)561325623, E-mail: ; and University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France

Received: 2015-10-01

Accepted: 2015-11-18

Published Online: 2015-12-19

Published in Print: 2016-04-01

Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 26, Issue 1, Pages 43–52, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: https://doi.org/10.1515/hmbci-2015-0045.

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