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Les adipokines : état des lieux et nouveautés

Adipokines: Current status and novelties

Résumé

Le tissu adipeux est reconnu en tant « qu’organe » capable de synthétiser et de sécréter plusieurs centaines de molécules qui exercent des actions pléiotropes, en particulier sur la régulation du métabolisme glucidolipidique, l’inflammation, l’angiogenèse ou la reproduction, molécules rassemblées sous le terme d’adipokines. De nombreux travaux ont été réalisés sur les adipokines « phares » que sont la leptine et l’adiponectine, notamment en raison de leur implication dans le métabolisme énergétique. Cependant, de nombreuses adipokines ont émergé depuis et représentent des cibles prometteuses, en particulier dans le contexte des désordres métaboliques associés à l’obésité. Dans cet article, nous ferons un point non exhaustif des adipokines « classiques » ou plus récemment découvertes dans le domaine de l’obésité et des maladies métaboliques.

Abstract

Adipose tissue is now recognized as an endocrine organ able to synthesize and secrete several hundred molecules molecules, which exert pleiotropic actions in particular on the regulation of carbohydrate and lipid metabolism, inflammation, angiogenesis, or reproduction. These molecules are gathered under the term adipokines. Many studies have been done on “leading” adipokines, leptin, and adiponectin, particularly because of their involvement in energy metabolism. However, many other adipokines have been more recently identified and represent promising targets in the context of metabolic disorders associated with obesity. In this review, we present a non-exhaustive point of “classic” and more recently discovered adipokines in the field of obesity and metabolic diseases.

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Références

  1. 1.

    Zhang Y, Proenca R, Maffei M, et al (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–32

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Lehr S, Hartwig S, Lamers D, et al (2012) Identification and validation of novel adipokines released from primary human adipocytes. Mol Cell Proteomics 11:M111.010504

  3. 3.

    Farooqi IS, Jebb SA, Langmack G, et al (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879–84

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Oral EA, Simha V, Ruiz E, et al (2002) Leptin replacement therapy for lipodystrophy. N Engl J Med 346:570–8

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Petersen KF, Oral EA, Dufour S, et al (2002) Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 109:1345–50

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Tong Q, Xu Y (2012) Central leptin regulation of obesity and fertility. Curr Obes Rep 1:236–4

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Poonpet T, Honsawek S (2014) Adipokines: biomarkers for osteoarthritis? World J Orthop 5:319–27

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Khan S, Shukla S, Sinha S, Meeran SM (2013) Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev 24:503–13

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Yamauchi T, Kamon J, Ito Y, et al (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–9

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Holland WL, Miller RA, Wang ZV, et al (2011) Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 17:55–63

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Berg AH, Combs TP, Du X, et al (2001) The adipocyte-secreted protein ACRP30 enhances hepatic insulin action. Nat Med 7:947–53

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Okada-Iwabu M, Yamauchi T, Iwabu M, et al (2013) A smallmolecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503:493–9

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Ohashi K, Shibata R, Murohara T, Ouchi N (2014) Role of anti-inflammatory adipokines in obesity-related diseases. Trends Endocrinol Metab 25:348–55

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Witberg G, Ayers CR, Turer AT, et al (2016) Relation of adiponectin to all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (from the Dallas Heart Study). Am J Cardiol 117:574–9

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Meyer M, Sellam J, Fellahi S, et al (2013) Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort. Arthritis Res Ther 15:R210

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Reverchon M, Rame C, Bertoldo M, Dupont J (2014) Adipokines and the female reproductive tract. Int J Endocrinol 2014:232454

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Grossmann ME, Cleary MP (2012) The balance between leptin and adiponectin in the control of carcinogenesis — focus on mammary tumorigenesis. Biochimie 94:2164–71

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Tatemoto K, Hosoya M, Habata Y, et al (1998) Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 251:471–6

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Castan-Laurell I, Dray C, Knauf C, et al (2012) Apelin, a promising target for type 2 diabetes treatment? Trends Endocrinol Metab 23:234–41

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Chapman NA, Dupré DJ, Rainey JK (2014) The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR. Biochem Cell Biol 92:431–40

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Knauf C, Drougard A, Fournel A, et al (2013) Hypothalamic actions of apelin on energy metabolism: new insight on glucose homeostasis and metabolic disorders. Horm Metab Res 45:928–34

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Boucher J, Masri B, Daviaud D, et al (2005) Apelin, a newly identified adipokine upregulated by insulin and obesity. Endocrinology 146:1764–71

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Castan-Laurell I, Dray C, Attané C, et al (2011) Apelin, diabetes, and obesity. Endocrine 40:1–9

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Ma WY, Yu TY, Wei JN, et al (2014) Plasma apelin: a novel biomarker for predicting diabetes. Clin Chim Acta 435:18–23

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Habchi M, Duvillard L, Cottet V, et al (2014) Circulating apelin is increased in patients with type 1 or type 2 diabetes and is associated with better glycemic control. Clin Endocrinol 81:696–701

    CAS  Article  Google Scholar 

  26. 26.

    Alexiadou K, Kokkinos A, Liatis S, et al (2012) Differences in plasma apelin and visfatin levels between patients with type 1 diabetes mellitus and healthy subjects and response after acute hyperglycemia and insulin administration. Hormones (Athens) 11:444–50

    Article  Google Scholar 

  27. 27.

    Krist J, Wieder K, Klöting N, et al (2013) Effects of weight loss and exercise on apelin serum concentrations and adipose tissue expression in human obesity. Obes Facts 6:57–69

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Heinonen MV, Laksonen DE, Karhu T, et al (2009) Effects of diet-induced weight loss on plasma apelin and cytokine levels in individuals with metabolic syndrome. Nutr Metab Cardiovasc Dis 19:626–33

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Adam F, Khatib AM, Lopez JJ, et al (2016) Apelin: an antithrombotic factor that inhibits platelet function. Blood 127:908–20

    Article  PubMed  Google Scholar 

  30. 30.

    Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesitylinked insulin resistance. Science 259:87–91

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–45

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Feve B, Bastard JP (2009) The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol 5:305–11

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Fain JN, Madan AK, Hiler ML, et al (2004) Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 145:2273–82

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–65

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Nieto-Vazquez I, Fernandez-Veledo S, de Alvaro C, Lorenzo M (2008) Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes 57:3211–21

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Wallenius V, Wallenius K, Ahren B, et al (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–9

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Grant RW, Dixit VD (2013) Mechanisms of disease: inflammasome activation and the development of type 2 diabetes. Front Immunol 4:50

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Bastard JP, Pieroni L, Hainque B (2000) Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance. Diabetes Metab Res Rev 16:192–201

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Morange PE, Alessi MC (2013) Thrombosis in central obesity and metabolic syndrome: mechanisms and epidemiology. Thromb Haemost 110:669–80

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Fukuhara A, Matsuda M, Nishizawa M, et al (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–30

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Fukuhara A, Matsuda M, Nishizawa M, et al (2007) Retraction. Science 318:565

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Friebe D, Neef M, Kratzsch J, et al (2011) Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (Nampt)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Diabetologia 54:1200–11

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Romacho T, Sanchez-Ferrer CF, Peiro C (2013) Visfatin/Nampt: an adipokine with cardiovascular impact. Mediators Inflamm 2013:946427

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Gosset M, Berenbaum F, Salvat C, et al (2008) Crucial role of visfatin/pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum 58:1399–409

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Steppan CM, Bailey ST, Bhat S, et al (2001) The hormone resistin links obesity to diabetes. Nature 409:307–12

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Park HK, Ahima RS (2013) Resistin in rodents and humans. Diabetes Metab J 37:404–14

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Hida K, Wada J, Eguchi J, et al (2005) Visceral adipose tissuederived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci USA 102:10610–5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Youn BS, Kloting N, Kratzsch J, et al (2008) Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 57:372–7

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Wittamer V, Franssen JD, Vulcano M, et al (2003) Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 198:977–85

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Goralski KB, Mc Carthy TC, Hanniman EA, et al (2007) Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 282:28175–88

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Rourke JL, Dranse HJ, Sinal CJ (2013) Towards an integrative approach to understanding the role of chemerin in human health and disease. Obes Rev 14:245–62

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Yang Q, Graham TE, Mody N, et al (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436:356–62

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Kotnik P, Fischer-Posovszky P, Wabitsch M (2011) RBP4: a controversial adipokine. Eur J Endocrinol 165:703–11

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Gaich G, Chien JY, Fu H, et al (2013) The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18:333–40

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Wang GX, Zhao XY, Meng ZX, et al (2014) The brown fatenriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med 20:1436–43

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Martinerie C, Garcia M, Huong Do TT, et al (2016) NOV/CCN3: a new adipocytokine involved in obesity-associated insulin resistance. Diabetes pii: db150617 [Epub ahead of print]

    Google Scholar 

  57. 57.

    Ota T (2013) Chemokine systems link obesity to insulin resistance. Diabetes Metab J 37:165–72

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Lafarge JC, Naour N, Clement K, Guerre-Millo M (2010) Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie 92:1580–6

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Taube A, Schlich R, Sell H, et al (2012) Inflammation and metabolic dysfunction: links to cardiovascular diseases. Am J Physiol Heart Circ Physiol 302:H2148–H65

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Cao H (2014) Adipocytokines in obesity and metabolic disease. J Endocrinol 220:T47–T59

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Jung UJ, Choi MS (2014) Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 15:6184–223

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Tabata M, Kadomatsu T, Fukuhara S, et al (2009) Angiopoietin like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. Cell Metab 10:178–88

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Stengel A, Tache Y (2011) Minireview: nesfatin-1 — an emerging new player in the braingut, endocrine, and metabolic axis. Endocrinology 152:4033–8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Bluher M (2014) Adipokines — removing road blocks to obesity and diabetes therapy. Mol Metab 3:230–40

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to J.-P. Bastard.

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Bastard, JP., Bastard, C., Fellahi, S. et al. Les adipokines : état des lieux et nouveautés. Obes 11, 181–193 (2016). https://doi.org/10.1007/s11690-016-0537-6

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Mots clés

  • Obésité
  • Adipokine
  • Tissu adipeux

Keywords

  • Obesity
  • Adipokine
  • Adipose tissue