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Adipocyte lipases and lipid droplet-associated proteins: insight from transgenic mouse models

International Journal of Obesity volume 36, pages 581–594 (2012)Cite this article

Abstract

Adipose tissue lipolysis is the catabolic process whereby stored triacylglycerol (TAG) is broken down by lipases into fatty acids and glycerol. Here, we review recent insights from transgenic mouse models. Genetic manipulations affecting lipases are considered first, followed by transgenic models of lipase co-factors and lastly non-lipase lipid droplet (LD)-associated proteins. The central role of hormone-sensitive lipase (HSL), long considered to be the sole rate-limiting enzyme of TAG hydrolysis, has been revised since the discovery of adipose triglyceride lipase (ATGL). It is now accepted that ATGL initiates TAG breakdown producing diacylglycerol, which is subsequently hydrolyzed by HSL. Furthermore, lipase activities are modulated by co-factors whose deletion causes severe metabolic disturbances. Another major advance has come from the description of the involvement of non-lipase proteins in the regulation of lipolysis. The role of perilipins has been extensively investigated. Other newly discovered LD-associated proteins have also been shown to regulate lipolysis.

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References

  1. Bezaire V, Langin D . Regulation of adipose tissue lipolysis revisited. Proc Nutr Soc 2009; 68: 350–360.

    Article  CAS  PubMed  Google Scholar 

  2. Lafontan M, Langin D . Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res 2009; 48: 275–297.

    Article  CAS  PubMed  Google Scholar 

  3. Brasaemle DL . Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J Lipid Res 2007; 48: 2547–2559.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Marcinkiewicz A, Gauthier D, Garcia A, Brasaemle DL . The phosphorylation of serine 492 of perilipin a directs lipid droplet fragmentation and dispersion. J Biol Chem 2006; 281: 11901–11909.

    Article  CAS  PubMed  Google Scholar 

  6. Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J et al. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. J Biol Chem 2009; 284: 18282–18291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Subramanian V, Rothenberg A, Gomez C, Cohen AW, Garcia A, Bhattacharyya S et al. Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes. J Biol Chem 2004; 279: 42062–42071.

    Article  CAS  PubMed  Google Scholar 

  8. Yamaguchi T, Omatsu N, Matsushita S, Osumi T . CGI-58 interacts with perilipin and is localized to lipid droplets. Possible involvement of CGI-58 mislocalization in Chanarin-Dorfman syndrome. J Biol Chem 2004; 279: 30490–30497.

    Article  CAS  PubMed  Google Scholar 

  9. Haemmerle G, Zimmermann R, Hayn M, Theussl C, Waeg G, Wagner E et al. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 2002; 277: 4806–4815.

    Article  CAS  PubMed  Google Scholar 

  10. Osuga J, Ishibashi S, Oka T, Yagyu H, Tozawa R, Fujimoto A et al. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci USA 2000; 97: 787–792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mulder H, Sorhede-Winzell M, Contreras JA, Fex M, Strom K, Ploug T et al. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact. J Biol Chem 2003; 278: 36380–36388.

    Article  CAS  PubMed  Google Scholar 

  12. Wang SP, Laurin N, Himms-Hagen J, Rudnicki MA, Levy E, Robert MF et al. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes Res 2001; 9: 119–128.

    Article  CAS  PubMed  Google Scholar 

  13. Fredrikson G, Tornqvist H, Belfrage P . Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochim Biophys Acta 1986; 876: 288–293.

    Article  CAS  PubMed  Google Scholar 

  14. Fortier M, Soni K, Laurin N, Wang SP, Mauriege P, Jirik FR et al. Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice. J Lipid Res 2005; 46: 1860–1867.

    Article  CAS  PubMed  Google Scholar 

  15. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347–2355.

    Article  CAS  PubMed  Google Scholar 

  16. Harada K, Shen WJ, Patel S, Natu V, Wang J, Osuga J et al. Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice. Am J Physiol Endocrinol Metab 2003; 285: E1182–E1195.

    Article  CAS  PubMed  Google Scholar 

  17. Park SY, Kim HJ, Wang S, Higashimori T, Dong J, Kim YJ et al. Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart. Am J Physiol Endocrinol Metab 2005; 289: E30–E39.

    Article  CAS  PubMed  Google Scholar 

  18. Fortier M, Wang SP, Mauriege P, Semache M, Mfuma L, Li H et al. Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading. Am J Physiol Endocrinol Metab 2004; 287: E282–E288.

    Article  CAS  PubMed  Google Scholar 

  19. Sekiya M, Osuga J, Okazaki H, Yahagi N, Harada K, Shen WJ et al. Absence of hormone-sensitive lipase inhibits obesity and adipogenesis in Lep ob/ob mice. J Biol Chem 2004; 279: 15084–15090.

    Article  CAS  PubMed  Google Scholar 

  20. Strom K, Hansson O, Lucas S, Nevsten P, Fernandez C, Klint C et al. Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice. PLoS One 2008; 3: e1793.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Zimmermann R, Haemmerle G, Wagner EM, Strauss JG, Kratky D, Zechner R . Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue. J Lipid Res 2003; 44: 2089–2099.

    Article  CAS  PubMed  Google Scholar 

  22. Shen WJ, Yu Z, Patel S, Jue D, Liu LF, Kraemer FB . Hormone-sensitive lipase modulates adipose metabolism through PPARgamma. Biochim Biophys Acta 2011; 1811: 9–16.

    Article  CAS  PubMed  Google Scholar 

  23. Okazaki H, Osuga J, Tamura Y, Yahagi N, Tomita S, Shionoiri F et al. Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases. Diabetes 2002; 51: 3368–3375.

    Article  CAS  PubMed  Google Scholar 

  24. Wood RJ . Vitamin D and adipogenesis: new molecular insights. Nutr Rev 2008; 66: 40–46.

    Article  PubMed  Google Scholar 

  25. Hansson O, Strom K, Guner N, Wierup N, Sundler F, Hoglund P et al. Inflammatory response in white adipose tissue in the non-obese hormone-sensitive lipase null mouse model. J Proteome Res 2006; 5: 1701–1710.

    Article  CAS  PubMed  Google Scholar 

  26. Strom K, Gundersen TE, Hansson O, Lucas S, Fernandez C, Blomhoff R et al. Hormone-sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL. FASEB J 2009; 23: 2307–2316.

    Article  PubMed  CAS  Google Scholar 

  27. Haemmerle G, Zimmermann R, Strauss JG, Kratky D, Riederer M, Knipping G et al. Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle. J Biol Chem 2002; 277: 12946–12952.

    Article  CAS  PubMed  Google Scholar 

  28. Voshol PJ, Haemmerle G, Ouwens DM, Zimmermann R, Zechner R, Teusink B et al. Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice. Endocrinology 2003; 144: 3456–3462.

    Article  CAS  PubMed  Google Scholar 

  29. Roduit R, Masiello P, Wang SP, Li H, Mitchell GA, Prentki M . A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice. Diabetes 2001; 50: 1970–1975.

    Article  CAS  PubMed  Google Scholar 

  30. Peyot ML, Nolan CJ, Soni K, Joly E, Lussier R, Corkey BE et al. Hormone-sensitive lipase has a role in lipid signaling for insulin secretion but is nonessential for the incretin action of glucagon-like peptide 1. Diabetes 2004; 53: 1733–1742.

    Article  CAS  PubMed  Google Scholar 

  31. Fex M, Haemmerle G, Wierup N, Dekker-Nitert M, Rehn M, Ristow M et al. A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis. Diabetologia 2009; 52: 271–280.

    Article  CAS  PubMed  Google Scholar 

  32. Lucas S, Tavernier G, Tiraby C, Mairal A, Langin D . Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis. J Lipid Res 2003; 44: 154–163.

    Article  CAS  PubMed  Google Scholar 

  33. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004; 306: 1383–1386.

    Article  CAS  PubMed  Google Scholar 

  34. Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW . Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem 2004; 279: 48968–48975.

    Article  CAS  PubMed  Google Scholar 

  35. Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS . Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 2004; 279: 47066–47075.

    Article  CAS  PubMed  Google Scholar 

  36. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006; 312: 734–737.

    Article  CAS  PubMed  Google Scholar 

  37. Schoiswohl G, Schweiger M, Schreiber R, Gorkiewicz G, Preiss-Landl K, Taschler U et al. Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids. J Lipid Res 2010; 51: 490–499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. Huijsman E, van de Par C, Economou C, van der Poel C, Lynch GS, Schoiswohl G et al. Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice. Am J Physiol Endocrinol Metab 2009; 297: E505–E513.

    Article  CAS  PubMed  Google Scholar 

  40. Peyot ML, Guay C, Latour MG, Lamontagne J, Lussier R, Pineda M et al. Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion. J Biol Chem 2009; 284: 16848–16859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kienesberger PC, Lee D, Pulinilkunnil T, Brenner DS, Cai L, Magnes C et al. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J Biol Chem 2009; 284: 30218–30229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ahmadian M, Duncan RE, Varady KA, Frasson D, Hellerstein MK, Birkenfeld AL et al. Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity. Diabetes 2009; 58: 855–866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kershaw EE, Hamm JK, Verhagen LA, Peroni O, Katic M, Flier JS . Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 2006; 55: 148–157.

    Article  CAS  PubMed  Google Scholar 

  44. Smirnova E, Goldberg EB, Makarova KS, Lin L, Brown WJ, Jackson CL . ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells. EMBO Rep 2006; 7: 106–113.

    Article  CAS  PubMed  Google Scholar 

  45. Tornqvist H, Nilsson-Ehle P, Belfrage P . Enzymes catalyzing the hydrolysis of long-chain monoacyglycerols in rat adipose tissue. Biochim Biophys Acta 1978; 530: 474–486.

    Article  CAS  PubMed  Google Scholar 

  46. 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: 27218–27223.

    Article  CAS  PubMed  Google Scholar 

  47. Taschler U, Radner FPW, Heier C, Schreiber R, Schweiger M, Schoiswohl G et al. Monoglyceride lipase-deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J Biol Chem 2011; 286: 17467–17477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG et al. Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci 2010; 13: 1113–1119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dolinsky VW, Gilham D, Alam M, Vance DE, Lehner R . Triacylglycerol hydrolase: role in intracellular lipid metabolism. Cell Mol Life Sci 2004; 61: 1633–1651.

    Article  CAS  PubMed  Google Scholar 

  50. Okazaki H, Igarashi M, Nishi M, Tajima M, Sekiya M, Okazaki S et al. Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis. Diabetes 2006; 55: 2091–2097.

    Article  CAS  PubMed  Google Scholar 

  51. Gao J, Simon M . Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase. J Invest Dermatol 2005; 124: 1259–1266.

    Article  CAS  PubMed  Google Scholar 

  52. Dolinsky VW, Sipione S, Lehner R, Vance DE . The cloning and expression of a murine triacylglycerol hydrolase cDNA and the structure of its corresponding gene. Biochim Biophys Acta 2001; 1532: 162–172.

    Article  CAS  PubMed  Google Scholar 

  53. Soni KG, Lehner R, Metalnikov P, O’Donnell P, Semache M, Gao W et al. Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase. J Biol Chem 2004; 279: 40683–40689.

    Article  CAS  PubMed  Google Scholar 

  54. Wei E, Gao W, Lehner R . Attenuation of adipocyte triacylglycerol hydrolase activity decreases basal fatty acid efflux. J Biol Chem 2007; 282: 8027–8035.

    Article  CAS  PubMed  Google Scholar 

  55. Schweiger M, Schreiber R, Haemmerle G, Lass A, Fledelius C, Jacobsen P et al. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J Biol Chem 2006; 281: 40236–40241.

    Article  CAS  PubMed  Google Scholar 

  56. Wei E, Ben Ali Y, Lyon J, Wang H, Nelson R, Dolinsky VW et al. Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure. Cell Metab 2010; 11: 183–193.

    Article  CAS  PubMed  Google Scholar 

  57. Lefevre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R et al. 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: 1002–1012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lass A, Zimmermann R, Haemmerle G, Riederer M, Schoiswohl G, Schweiger M et al. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab 2006; 3: 309–319.

    Article  CAS  PubMed  Google Scholar 

  59. 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: 34538–34544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 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: 5726–5735.

    Article  CAS  PubMed  Google Scholar 

  61. Yamaguchi T, Omatsu N, Morimoto E, Nakashima H, Ueno K, Tanaka T et al. CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation. J Lipid Res 2007; 48: 1078–1089.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Radner FP, Streith IE, Schoiswohl G, Schweiger M, Kumari M, Eichmann TO et al. Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58). J Biol Chem 2010; 285: 7300–7311.

    Article  CAS  PubMed  Google Scholar 

  64. Brasaemle DL . Lipolysis control: the plot thickens. Cell Metab 2010; 11: 173–174.

    Article  CAS  PubMed  Google Scholar 

  65. Hertzel AV, Bennaars-Eiden A, Bernlohr DA . Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells. J Lipid Res 2002; 43: 2105–2111.

    Article  CAS  PubMed  Google Scholar 

  66. Maeda K, Uysal KT, Makowski L, Gorgun CZ, Atsumi G, Parker RA et al. Role of the fatty acid binding protein mal1 in obesity and insulin resistance. Diabetes 2003; 52: 300–307.

    Article  CAS  PubMed  Google Scholar 

  67. Jenkins-Kruchten AE, Bennaars-Eiden A, Ross JR, Shen WJ, Kraemer FB, Bernlohr DA . Fatty acid-binding protein-hormone-sensitive lipase interaction. Fatty acid dependence on binding. J Biol Chem 2003; 278: 47636–47643.

    Article  CAS  PubMed  Google Scholar 

  68. Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB . Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. Proc Natl Acad Sci USA 1999; 96: 5528–5532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Smith AJ, Sanders MA, Thompson BR, Londos C, Kraemer FB, Bernlohr DA . Physical association between the adipocyte fatty acid-binding protein and hormone-sensitive lipase: a fluorescence resonance energy transfer analysis. J Biol Chem 2004; 279: 52399–52405.

    Article  CAS  PubMed  Google Scholar 

  70. Smith AJ, Thompson BR, Sanders MA, Bernlohr DA . Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase: regulation by fatty acids and phosphorylation. J Biol Chem 2007; 282: 32424–32432.

    Article  CAS  PubMed  Google Scholar 

  71. Hotamisligil GS, Johnson RS, Distel RJ, Ellis R, Papaioannou VE, Spiegelman BM . Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274: 1377–1379.

    Article  CAS  PubMed  Google Scholar 

  72. Coe NR, Simpson MA, Bernlohr DA . Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J Lipid Res 1999; 40: 967–972.

    CAS  PubMed  Google Scholar 

  73. Baar RA, Dingfelder CS, Smith LA, Bernlohr DA, Wu C, Lange AJ et al. Investigation of in vivo fatty acid metabolism in AFABP/aP2(−/−) mice. Am J Physiol Endocrinol Metab 2005; 288: E187–E193.

    Article  CAS  PubMed  Google Scholar 

  74. Uysal KT, Scheja L, Wiesbrock SM, Bonner-Weir S, Hotamisligil GS . Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 2000; 141: 3388–3396.

    Article  CAS  PubMed  Google Scholar 

  75. Kimmel AR, Brasaemle DL, McAndrews-Hill M, Sztalryd C, Londos C . Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J Lipid Res 2010; 51: 468–471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Martinez-Botas J, Anderson JB, Tessier D, Lapillonne A, Chang BH, Quast MJ et al. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nat Genet 2000; 26: 474–479.

    Article  CAS  PubMed  Google Scholar 

  77. Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O et al. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci USA 2001; 98: 6494–6499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Castro-Chavez F, Yechoor VK, Saha PK, Martinez-Botas J, Wooten EC, Sharma S et al. Coordinated upregulation of oxidative pathways and downregulation of lipid biosynthesis underlie obesity resistance in perilipin knockout mice: a microarray gene expression profile. Diabetes 2003; 52: 2666–2674.

    Article  CAS  PubMed  Google Scholar 

  79. Saha PK, Kojima H, Martinez-Botas J, Sunehag AL, Chan L . Metabolic adaptations in the absence of perilipin: increased beta-oxidation and decreased hepatic glucose production associated with peripheral insulin resistance but normal glucose tolerance in perilipin-null mice. J Biol Chem 2004; 279: 35150–35158.

    Article  CAS  PubMed  Google Scholar 

  80. Miyoshi H, Souza SC, Endo M, Sawada T, Perfield II JW, Shimizu C et al. Perilipin overexpression in mice protects against diet-induced obesity. J Lipid Res 2010; 51: 975–982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sawada T, Miyoshi H, Shimada K, Suzuki A, Okamatsu-Ogura Y, Perfield II JW et al. Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype. PLoS One 2011; 5: e14006.

    Article  CAS  Google Scholar 

  82. Chang BH, Li L, Paul A, Taniguchi S, Nannegari V, Heird WC et al. Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein. Mol Cell Biol 2006; 26: 1063–1076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bell M, Wang H, Chen H, McLenithan JC, Gong DW, Yang RZ et al. Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance. Diabetes 2008; 57: 2037–2045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Beller M, Sztalryd C, Southall N, Bell M, Jackle H, Auld DS et al. COPI complex is a regulator of lipid homeostasis. PLoS Biol 2008; 6: e292.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Inohara N, Koseki T, Chen S, Wu X, Nunez G . CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. EMBO J 1998; 17: 2526–2533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhou Z, Yon Toh S, Chen Z, Guo K, Ng CP, Ponniah S et al. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat Genet 2003; 35: 49–56.

    Article  PubMed  CAS  Google Scholar 

  87. Li JZ, Ye J, Xue B, Qi J, Zhang J, Zhou Z et al. Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation. Diabetes 2007; 56: 2523–2532.

    Article  CAS  PubMed  Google Scholar 

  88. Qi J, Gong J, Zhao T, Zhao J, Lam P, Ye J et al. Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. EMBO J 2008; 27: 1537–1548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ye J, Li JZ, Liu Y, Li X, Yang T, Ma X et al. Cideb, an ER- and lipid droplet-associated protein, mediates VLDL lipidation and maturation by interacting with apolipoprotein B. Cell Metab 2009; 9: 177–190.

    Article  CAS  PubMed  Google Scholar 

  90. Danesch U, Hoeck W, Ringold GM . Cloning and transcriptional regulation of a novel adipocyte-specific gene, FSP27. CAAT-enhancer-binding protein (C/EBP) and C/EBP-like proteins interact with sequences required for differentiation-dependent expression. J Biol Chem 1992; 267: 7185–7193.

    CAS  PubMed  Google Scholar 

  91. Puri V, Konda S, Ranjit S, Aouadi M, Chawla A, Chouinard M et al. Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage. J Biol Chem 2007; 282: 34213–34218.

    Article  CAS  PubMed  Google Scholar 

  92. Toh SY, Gong J, Du G, Li JZ, Yang S, Ye J et al. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice. PLoS One 2008; 3: e2890.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Nishino N, Tamori Y, Tateya S, Kawaguchi T, Shibakusa T, Mizunoya W et al. FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest 2008; 118: 2808–2821.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Langin D . Recruitment of brown fat and conversion of white into brown adipocytes: strategies to fight the metabolic complications of obesity? Biochim Biophys Acta 2010; 1801: 372–376.

    Article  CAS  PubMed  Google Scholar 

  95. Farese Jr RV, Walther TC . Lipid droplets finally get a little R-E-S-P-E-C-T. Cell 2009; 139: 855–860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ross SR, Graves RA, Greenstein A, Platt KA, Shyu HL, Mellovitz B et al. A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo. Proc Natl Acad Sci USA 1990; 87: 9590–9594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Martens K, Bottelbergs A, Baes M . Ectopic recombination in the central and peripheral nervous system by aP2/FABP4-Cre mice: implications for metabolism research. FEBS Lett 2010; 584: 1054–1058.

    Article  CAS  PubMed  Google Scholar 

  98. Urs S, Harrington A, Liaw L, Small D . Selective expression of an aP2/Fatty Acid Binding Protein 4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Res 2006; 15: 647–653.

    Article  CAS  PubMed  Google Scholar 

  99. Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA et al. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 2001; 7: 699–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Mao J, Yang T, Gu Z, Heird WC, Finegold MJ, Lee B et al. aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues. Proc Natl Acad Sci USA 2009; 106: 17576–17581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Van Dyck F, Scroyen I, Declercq J, Sciot R, Kahn B, Lijnen R et al. aP2-Cre-mediated expression activation of an oncogenic PLAG1 transgene results in cavernous angiomatosis in mice. Int J Oncol 2008; 32: 33–40.

    CAS  PubMed  Google Scholar 

  102. Wang ZV, Deng Y, Wang QA, Sun K, Scherer PE . Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression. Endocrinology 2010; 151: 2933–2939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Langin D, Dicker A, Tavernier G, Hoffstedt J, Mairal A, Ryden M et al. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 2005; 54: 3190–3197.

    Article  CAS  PubMed  Google Scholar 

  104. Jocken JW, Langin D, Smit E, Saris WH, Valle C, Hul GB et al. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab 2007; 92: 2292–2299.

    Article  CAS  PubMed  Google Scholar 

  105. Ahren B . Reducing plasma free fatty acids by acipimox improves glucose tolerance in high-fat fed mice. Acta Physiol Scand 2001; 171: 161–167.

    Article  CAS  PubMed  Google Scholar 

  106. Wang M, Fotsch C . Small-molecule compounds that modulate lipolysis in adipose tissue: targeting strategies and molecular classes. Chem Biol 2006; 13: 1019–1027.

    Article  CAS  PubMed  Google Scholar 

  107. Ebdrup S, Refsgaard HH, Fledelius C, Jacobsen P . Synthesis and structure-activity relationship for a novel class of potent and selective carbamate-based inhibitors of hormone selective lipase with acute in vivo antilipolytic effects. J Med Chem 2007; 50: 5449–5456.

    Article  CAS  PubMed  Google Scholar 

  108. Long JZ, Nomura DK, Cravatt BF . Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism. Chem Biol 2009; 16: 744–753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Gilham D, Ho S, Rasouli M, Martres P, Vance DE, Lehner R . Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion. FASEB J 2003; 17: 1685–1687.

    Article  CAS  PubMed  Google Scholar 

  110. Leung D, Hardouin C, Boger DL, Cravatt BF . Discovering potent and selective reversible inhibitors of enzymes in complex proteomes. Nat Biotechnol 2003; 21: 687–691.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

AG was supported by INSERM and the Fondation pour la Recherche Médicale (http://www.frm.org). The laboratory of the authors was supported by Inserm, Fondation pour la Recherche Médicale and the Commission of the European Communities (Integrated Project HEPADIP (www.hepadip.org), Contract No. LSH-2003-1.1.3-1, and Collaborative Project ADAPT (www.adapt-eu.net), Contract No. HEALTH-F2-2008-2011 00). The authors deeply thank Dr DB Savage (Institute of Metabolic Science, University of Cambridge, UK) for critical reading of the paper.

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  1. Laboratoire de Recherche sur les Obésités, INSERM U1048-I2MC, Equipe 4, Toulouse, France

    A Girousse & D Langin

  2. University Paul Sabatier, Toulouse, France

    A Girousse & D Langin

  3. Laboratoire de Biochimie, Institut Fédératif de Biologie, CHU de Toulouse, France

    D Langin

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  1. A Girousse
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  2. D Langin
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Correspondence to D Langin.

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Girousse, A., Langin, D. Adipocyte lipases and lipid droplet-associated proteins: insight from transgenic mouse models. Int J Obes 36, 581–594 (2012). https://doi.org/10.1038/ijo.2011.113

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