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Physiologie et physiopathologie du tissu adipeux pp 143–160Cite as

La lipolyse adipocytaire

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Résumé

Le tissu adipeux (TA) blanc est le principal lieu de stockage énergétique chez les mammifères. Il joue un rôle crucial dans la balance énergétique aussi bien au niveau cellulaire que de l’organisme entier, stockant l’énergie sous forme de triacylglycérols (ou triglycérides, TG) après les repas et les libérant pour les autres organes sous la forme d’acides gras (AG) non estérifiés durant le jeûne ou l’exercice. De ce fait, les voies de signalisation contrôlant l’accumulation des graisses (consommation cellulaire d’AG, lipogenèse de novo et estérification en TG) et leur mobilisation (lipolyse) dans les adipocytes sont étroitement corégulées. Alors que la synthèse des TG se produit dans plusieurs tissus, tels que le foie pour la production de lipoprotéines à basse densité, la lipolyse permettant la libération des AG comme source d’énergie pour les autres tissus est uniquement imputable aux cellules adipeuses (adipocytes). La compréhension des acteurs cellulaires et moléculaires régulant ces processus métaboliques est en constante progression. Des découvertes récentes ont démontré l’importance de nouveaux acteurs moléculaires dans la régulation de la lipolyse. élucider les modes de fonctionnement de ces nouvelles voies pourrait conduire à de nouvelles cibles thérapeutiques visant au traitement de l’obésité et des désordres métaboliques qui lui sont associés.

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Références

  1. Bartness TJ, Shrestha YB, Vaughan CH et al. (2010) Sensory and sympathetic nervous system control of white adipose tissue lipolysis. Molecular and cellular endocrinology 318: 34–43

    Article  PubMed  CAS  Google Scholar 

  2. Scherer T, O’Hare J, Diggs-Andrews K et al. (2011) Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell metabolism 13: 183–94

    Article  PubMed  CAS  Google Scholar 

  3. Lafontan M, Berlan M (1993) Fat cell adrenergic receptors and the control of white and brown fat cell function. J. Lipid. Res. 34: 1057–91

    PubMed  CAS  Google Scholar 

  4. Tavernier G, Jimenez M, Giacobino JP et al. (2005) Norepinephrine induces lipolysis in beta1/beta2/beta3-adrenoceptor knockout mice. Mol Pharmacol 68: 793–9

    PubMed  CAS  Google Scholar 

  5. Langin D (2006) Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol Res 53: 482–91

    Article  PubMed  CAS  Google Scholar 

  6. Lönnqvist F, Krief S, Strosberg AD et al. (1993) Evidence for a functional b3-adrenoceptor in man. Br. J. Pharmacol 110: 929–36

    Article  PubMed  Google Scholar 

  7. Lafontan M, Berlan M (1995) Fat cell α2-adrenoceptors: the regulation of fat cell function and lipolysis. Endocrine Rev 16: 716–38

    CAS  Google Scholar 

  8. Ahmed K, Tunaru S, Offermanns S (2009) GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol Sci 30: 557–62

    Article  PubMed  CAS  Google Scholar 

  9. Ahmed K, Tunaru S, Tang C et al. (2010) An autocrine lactate loop mediates insulindependent inhibition of lipolysis through GPR81. Cell metabolism 11: 311–9

    Article  PubMed  CAS  Google Scholar 

  10. Langin D (2010) Adipose tissue lipolysis revisited (again!): lactate involvement in insulin antilipolytic action. Cell Metab 11: 242–3

    Article  PubMed  CAS  Google Scholar 

  11. Ge H, Li X, Weiszmann J et al. (2008) Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology 149: 4519–26

    Article  PubMed  CAS  Google Scholar 

  12. Hirasawa A, Hara T, Katsuma S et al. (2008) Free fatty acid receptors and drug discovery. Biol Pharm Bull 31: 1847–51

    Article  PubMed  CAS  Google Scholar 

  13. Lafontan M, Langin D (2009) Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res 48: 275–97

    Article  PubMed  CAS  Google Scholar 

  14. Turtzo LC, Marx R, Lane MD (2001) Cross-talk between sympathetic neurons and adipocytes in coculture. Proc Natl Acad Sci États-Unis 98: 12385–90

    Article  CAS  Google Scholar 

  15. Kos K, Baker AR, Jernas M et al. (2009) DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue. Diabetes Obes Metab 11: 285–92

    Article  PubMed  CAS  Google Scholar 

  16. Jaworski K, Ahmadian M, Duncan RE et al. (2009) AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat Med 15: 159–68

    Article  PubMed  CAS  Google Scholar 

  17. Lafontan M, Moro C, Sengenes C et al. (2005) An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans. Arterioscler Thromb Vasc Biol 25: 2032–42

    Article  PubMed  CAS  Google Scholar 

  18. Choi YH, Park S, Hockman S et al. (2006) Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. J Clin Invest 116: 3240–51

    Article  PubMed  CAS  Google Scholar 

  19. Moller N, Jorgensen JO (2009) Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30: 152–77

    Article  PubMed  Google Scholar 

  20. Langin D, Arner P (2006) Importance of TNFalpha and neutral lipases in human adipose tissue lipolysis. Trends Endocrinol Metab 17: 314–20

    Article  PubMed  CAS  Google Scholar 

  21. Plomgaard P, Fischer CP, Ibfelt T et al. (2008) Tumor necrosis factor-alpha modulates human in vivo lipolysis. The Journal of clinical endocrinology and metabolism 93: 543–9

    Article  PubMed  CAS  Google Scholar 

  22. Bing C (2011) Lipid mobilization in cachexia: mechanisms and mediators. Curr Opin Support Palliat Care 5: 356–60

    PubMed  Google Scholar 

  23. Girousse A, Langin D (2011) Adipocyte lipases and lipid droplet-associated proteins: insight from transgenic mouse models. Int J Obes (Lond) Jun 14._doi: 10.1038/ ijo.2011.113._[Epub ahead of print]

    Google Scholar 

  24. Ribet C, Montastier E, Valle C et al. (2010) PPARalpha control of lipid and glucose metabolism in human white adipocytes. Endocrinology 151: 123–33

    Article  PubMed  CAS  Google Scholar 

  25. Mazzucotelli A, Viguerie N, Tiraby C et al. (2007) The Transcriptional Coactivator PGC-1alpha and the Nuclear Receptor PPARalpha Control the Expression of Glycerol Kinase and Metabolism Genes Independently of PPARgamma Activation in Human White Adipocytes. Diabetes 56: 2467–75

    Article  PubMed  CAS  Google Scholar 

  26. Brasaemle DL (2007) Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J Lipid Res 48: 2547–59

    Article  PubMed  CAS  Google Scholar 

  27. Bezaire V, Langin D (2009) Regulation of adipose tissue lipolysis revisited. Proc. Nutr. Soc. 68: 350–60

    Article  PubMed  CAS  Google Scholar 

  28. Kolditz CI, Langin D (2010) Adipose tissue lipolysis. Curr Opin Clin Nutr Metab Care 13: 377–81

    Article  PubMed  CAS  Google Scholar 

  29. Krintel C, Osmark P, Larsen MR et al. (2008) Ser649 and Ser650 are the major determinants of protein kinase A-mediated activation of human hormone-sensitive lipase against lipid substrates. PLoS One 3: e3756

    Article  PubMed  Google Scholar 

  30. Krintel C, Morgelin M, Logan DT, Holm C (2009) Phosphorylation of hormonesensitive lipase by protein kinase A in vitro promotes an increase in its hydrophobic surface area. Febs J 276: 4752–62

    Article  PubMed  CAS  Google Scholar 

  31. Strom K, Hansson O, Lucas S et al. (2008) Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice. PLoS ONE 3: e1793

    Article  PubMed  Google Scholar 

  32. Shen WJ, Yu Z, Patel S et al. (2011) Hormone-sensitive lipase modulates adipose metabolism through PPARgamma. Biochim Biophys Acta 1811: 9–16

    Article  PubMed  CAS  Google Scholar 

  33. Zimmermann R, Lass A, Haemmerle G, Zechner R (2009) Fate of fat: The role of adipose triglyceride lipase in lipolysis. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 1791: 494–500

    Article  CAS  Google Scholar 

  34. Strom K, Gundersen TE, Hansson O et al. (2009) Hormone-sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL. FASEB J 23: 2307–16

    Article  PubMed  Google Scholar 

  35. Zechner R, Kienesberger PC, Haemmerle G et al. (2009) Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res 50: 3–21

    Article  PubMed  CAS  Google Scholar 

  36. Schweiger M, Schoiswohl G, Lass A et al. (2008) The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding. J Biol Chem 283: 17211–20

    Article  PubMed  CAS  Google Scholar 

  37. Zimmermann R, Strauss JG, Haemmerle G et al. (2004) Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306: 1383–6

    Article  PubMed  CAS  Google Scholar 

  38. Ahmadian M, Duncan RE, Varady KA et al. (2009) Adipose Overexpression of Desnutrin Promotes Fatty Acid Use and Attenuates Diet-Induced Obesity. Diabetes 58: 855–66

    Article  PubMed  CAS  Google Scholar 

  39. Bezaire V, Mairal A, Ribet C et al. (2009) Contribution of Adipose Triglyceride Lipase and Hormone-sensitive Lipase to Lipolysis in hMADS Adipocytes. J Biol Chem 284: 18282–91

    Article  PubMed  CAS  Google Scholar 

  40. Haemmerle G, Lass A, Zimmermann R et al. (2006) Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312: 734–7

    Article  PubMed  CAS  Google Scholar 

  41. Schoiswohl G, Schweiger M, Schreiber R et al. (2010) Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids. J Lipid Res 51: 490–9

    Article  PubMed  CAS  Google Scholar 

  42. Huijsman E, van de Par C, Economou C et al. (2009) Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice. Am J Physiol Endocrinol Metab 297: E505–13

    Article  PubMed  CAS  Google Scholar 

  43. Ahmadian M, Abbott MJ, Tang T et al. (2011) Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype. Cell metabolism 13: 739–48

    Article  PubMed  CAS  Google Scholar 

  44. Taschler U, Radner FPW, Heier C et al. (2011) Monoglyceride lipase-deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J Biol Chem 286: 17467–77

    Article  PubMed  CAS  Google Scholar 

  45. Furuhashi M, Hotamisligil GS (2008) Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 7: 489–503

    Article  PubMed  CAS  Google Scholar 

  46. Scheja L, Makowski L, Uysal KT et al. (1999) Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/-mice. Diabetes 48: 1987–94

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  48. Smith AJ, Thompson BR, Sanders MA, Bernlohr DA (2007) Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase: regulation by fatty acids and phosphorylation. J Biol Chem 282: 32424–32

    Article  PubMed  CAS  Google Scholar 

  49. Furuhashi M, Fucho R, Gorgun CZ et al. (2008) Adipocyte/macrophage fatty acidbinding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest 118: 2640–50

    PubMed  CAS  Google Scholar 

  50. Lan H, Cheng CC, Kowalski TJ et al. (2011) Small-molecule inhibitors of FABP4/5 ameliorate dyslipidemia but not insulin resistance in mice with diet-induced obesity. Journal of lipid research 52: 646–56

    Article  PubMed  CAS  Google Scholar 

  51. Lass A, Zimmermann R, Haemmerle G et al. (2006) Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab 3: 309–19

    Article  PubMed  CAS  Google Scholar 

  52. Miyoshi H, Perfield JW, Souza SC et al. (2007) Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes. J Biol Chem 282: 996–1002

    Article  PubMed  CAS  Google Scholar 

  53. Granneman JG, Moore HP, Granneman RL et al. (2007) Analysis of lipolytic protein trafficking and interactions in adipocytes. J Biol Chem 282: 5726–35

    Article  PubMed  CAS  Google Scholar 

  54. Yamaguchi T, Omatsu N, Morimoto E et al. (2007) CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation. J Lipid Res 48: 1078–89

    Article  PubMed  CAS  Google Scholar 

  55. Radner FP, Streith IE, Schoiswohl G et al. (2010) Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58). J Biol Chem 285: 7300–11

    Article  PubMed  CAS  Google Scholar 

  56. Yang X, Lu X, Lombes M et al. (2010) The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab 11: 194–205

    Article  PubMed  CAS  Google Scholar 

  57. Brasaemle DL, Subramanian V, Garcia A et al. (2009) Perilipin A and the control of triacylglycerol metabolism. Mol Cell Biochem 326: 15–21

    Article  PubMed  CAS  Google Scholar 

  58. Ducharme NA, Bickel PE (2008) Lipid droplets in lipogenesis and lipolysis. Endocrinology 149: 942–9

    Article  PubMed  CAS  Google Scholar 

  59. Granneman J, Moore H, Krishnamoorthy R, Rathod M (2009) Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). Journal of Biological Chemistry 284: 34538–44

    Article  PubMed  CAS  Google Scholar 

  60. Granneman JG, Moore HP, Mottillo EP et al. (2011) Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase. J Biol Chem 286: 5126–35

    Article  PubMed  CAS  Google Scholar 

  61. Pilch PF, Souto RP, Liu L et al. (2007) Cellular spelunking: exploring adipocyte caveolae. J Lipid Res 48: 2103–11

    Article  PubMed  CAS  Google Scholar 

  62. Cohen AW, Razani B, Schubert W et al. (2004) Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53: 1261–70

    Article  PubMed  CAS  Google Scholar 

  63. Vigouroux, Caron-Debarle M, Le Dour C et al. 2011. Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity. Int J Biochem Cell Biol 43: 862–76

    Article  PubMed  CAS  Google Scholar 

  64. Nordstrom EA, Ryden M, Backlund EC et al. (2005) A human-specific role of cell deathinducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity. Diabetes 54: 1726–34

    Article  PubMed  Google Scholar 

  65. Puri V, Ranjit S, Konda S et al. (2008) Cidea is associated with lipid droplets and insulin sensitivity in humans. Proc Natl Acad Sci U S A 105: 7833–8

    Article  PubMed  CAS  Google Scholar 

  66. Zhou Z, Yon Toh S, Chen Z et al. (2003) Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat Genet 35: 49–56

    Article  PubMed  Google Scholar 

  67. Magnusson B, Gummesson A, Glad CA et al. (2008) Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism. Metabolism 57: 1307–13

    Article  PubMed  CAS  Google Scholar 

  68. Nishino N, Tamori Y, Tateya S et al. (2008) FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest 118: 2808–21

    PubMed  CAS  Google Scholar 

  69. Toh SY, Gong J, Du G et al. (2008) Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice. PLoS One 3: e2890

    Article  PubMed  Google Scholar 

  70. Arner P, Bernard S, Salehpour M et al. (2011) Dynamics of human adipose lipid turnover in health and metabolic disease. Nature 478: 110–3

    Article  PubMed  CAS  Google Scholar 

  71. Langin D (2011) In and out: adipose tissue lipid turnover in obesity and dyslipidemia. Cell Metab 14: 569–70

    Article  PubMed  CAS  Google Scholar 

  72. Virtue S, Vidal-Puig A (2008) It’s not how fat you are, it’s what you do with it that counts. PLoS biology 6: e237

    Article  PubMed  Google Scholar 

  73. McQuaid SE, Hodson L, Neville MJ et al. (2011) Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition? Diabetes 60: 47–55

    Article  PubMed  CAS  Google Scholar 

  74. Samuel VT, Petersen KF, Shulman GI (2010) Lipid-induced insulin resistance: unravelling the mechanism. Lancet 375: 2267–77

    Article  PubMed  CAS  Google Scholar 

  75. Karpe F, Dickmann JR, Frayn KN (2011) Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 60: 2441–9

    Article  PubMed  CAS  Google Scholar 

  76. Bartness TJ, Song CK (2007) Thematic review series: adipocyte biology. Sympathetic and sensory innervation of white adipose tissue. J Lipid Res 48: 1655–72

    Article  PubMed  CAS  Google Scholar 

  77. Lafontan M, Moro C, Berlan M et al. (2008) Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol Metab 19: 130–7

    Article  PubMed  CAS  Google Scholar 

  78. Langin D (2010) Recruitment of brown fat and conversion of white into brown adipocytes: Strategies to fight the metabolic complications of obesity? Biochim Biophys Acta 1801: 372–6

    Article  PubMed  CAS  Google Scholar 

  79. Wang M, Fotsch C (2006) Small-molecule compounds that modulate lipolysis in adipose tissue: targeting strategies and molecular classes. Chem Biol 13: 1019–27

    Article  PubMed  CAS  Google Scholar 

  80. Lukasova M, Hanson J, Tunaru S, Offermanns S (2011) Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potentials. Trends Pharmacol Sci 32:700–7

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Service de Biochimie, Hôpitaux de Toulouse, France

    D. Langin

  2. Inserm, UMR1048, Laboratoire de Recherche sur les Obésités Éequipe 4, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 1, avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France

    E. Mouisel & D. Langin

  3. UMR1048, Université Paul Sabatier, Université de Toulouse, Toulouse, France

    E. Mouisel & D. Langin

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Mouisel, E., Langin, D. (2013). La lipolyse adipocytaire. In: Physiologie et physiopathologie du tissu adipeux. Springer, Paris. https://doi.org/10.1007/978-2-8178-0332-6_10

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  • DOI: https://doi.org/10.1007/978-2-8178-0332-6_10

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