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Syndromes lipodystrophiques génétiques et acquis

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Physiologie et physiopathologie du tissu adipeux

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Résumé

Une augmentation de la masse grasse, telle qu’observée au cours de l’obésité androïde et du syndrome métabolique, est clairement associée à des complications métaboliques. Cependant, à l’inverse, l’absence ou la perte de tissu adipeux (TA) lié aux lipodystrophies, qu’elles soient d’origine génétique ou acquise, conduisent à des atteintes métaboliques encore plus sévères, associées à des complications précoces. Ces dernières années, l’étiologie génétique d’un certain nombre de syndromes lipodystrophiques a été élucidée [1–9], soulignant ainsi le rôle majeur de plusieurs protéines dans la physiologie du TA. Les syndromes lipodystrophiques acquis, quant à eux, peuvent être d’origine iatrogène, liés à certains traitements, antirétroviraux de l’infection VIH ou aux glucocorticoïdes, ces formes étant assez communes, ou encore associés à des dérèglements endocrines ou immunitaires.

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Références

  1. Barroso I, Gurnell M, Crowley VE et al. (1999) Dominant negative mutations in human PPAR g associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402: 880–3

    PubMed  CAS  Google Scholar 

  2. Cao H, Hegele RA (2000) Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 9: 109–12

    Article  PubMed  CAS  Google Scholar 

  3. Magré J, Delépine M, Khallouf E et al. (2001) Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nature Genet 28: 365–70

    Article  PubMed  Google Scholar 

  4. Agarwal AK, Arioglu E, De Almeida S et al. (2002) AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nature Genet 31: 21–3

    Article  PubMed  CAS  Google Scholar 

  5. George S, Rochford JJ, Wolfrum C et al. (2004) A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science 304: 1325–8

    Article  PubMed  CAS  Google Scholar 

  6. Kim C, Delépine M, Boutet E et al. (2008) Association of a homozygous nonsense Caveolin-1 mutation with Berardinelli-Seip Congenital Lipodystrophy. J Clin Endocrinol Metab 93: 1129–34

    Article  PubMed  CAS  Google Scholar 

  7. Hayashi YK, Matsuda C, Ogawa M et al. (2009) Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest 119: 2623–33

    Article  PubMed  CAS  Google Scholar 

  8. Rubio-Cabezas O, Puri V, Murano I et al. (2009) Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Mol Med 1: 280–7

    Article  PubMed  CAS  Google Scholar 

  9. Gandotra S, Le Dour C, Bottomley W et al. (2011) Perilipin deficiency and autosomal dominant partial lipodystrophy. NEJM 364: 740–8

    Article  PubMed  CAS  Google Scholar 

  10. Garg A (2011) Lipodystrophies: Genetic and Acquired Body Fat Disorders. J Clin Endocrinol Metab 96: 3313–25

    Article  PubMed  CAS  Google Scholar 

  11. Vigouroux C, 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 

  12. Misra A, Peethambaram A, Garg A (2004) Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine (Baltimore) 83: 18–34

    Article  CAS  Google Scholar 

  13. Virtue S, Vidal-Puig A (2010) Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome—an allostatic perspective. Biochim Biophys Acta 1801: 338–49

    Article  PubMed  CAS  Google Scholar 

  14. Semple RK, Cochran EK, Soos MA et al. (2008) Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance. Diabetes Care 31: 977–9

    Article  PubMed  CAS  Google Scholar 

  15. Gale SE, Frolov A, Han X et al. (2006) A regulatory role for 1-acylglycerol-3-phosphate-O-acyltransferase 2 in adipocyte differentiation. J Biol Chem 281: 11082–9

    Article  PubMed  CAS  Google Scholar 

  16. Van Maldergem L, Magré J, Gedde-Dahl Jr T et al. (2002) Genotype-Phenotype Relationships in Berardinelli-Seip Congenital Lipodystrophy. J Med Genet 39: 722–33

    Article  PubMed  Google Scholar 

  17. Simha V, Garg A (2003) Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or Seipin genes. J Clin Endocrinol Metab 88: 5433–7

    Article  PubMed  CAS  Google Scholar 

  18. Antuna-Puente B, Boutet E, Vigouroux C et al. (2010) Higher adiponectin levels in patients with Berardinelli-Seip congenital lipodystrophy due to seipin as compared with 1-acylglycerol-3-phosphate-o-acyltransferase-2 deficiency. J Clin Endocrinol Metab 95: 1463–8

    Article  PubMed  CAS  Google Scholar 

  19. Szymanski KM, Binns D, Bartz R et al. (2007) The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc Natl Acad Sci états-Unis 104: 20890–5

    Article  CAS  Google Scholar 

  20. Binns DD, Lee S, Hilton CL et al. (2010) Seipin is a discrete homooligomer. Biochemistry 49: 10747–55

    Article  PubMed  CAS  Google Scholar 

  21. Boutet E, El Mourabit H, Prot M et al. (2009) Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy. Biochimie 91: 796–803

    Article  PubMed  CAS  Google Scholar 

  22. Cao H, Alston L, Ruschman J et al. (2008) Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. Lipids Health Dis 7: 3

    Article  PubMed  Google Scholar 

  23. Blouin CM, Le Lay S, Eberl A et al. (2010) Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects. J Lipid Res 51: 945–56

    Article  PubMed  CAS  Google Scholar 

  24. Le Lay S, Briand N, Blouin CM et al. (2010) The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes. Autophagy 6: 754–63

    Article  PubMed  CAS  Google Scholar 

  25. Hill MM, Bastiani M, Luetterforst R et al. (2008) PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132: 113–24

    Article  PubMed  CAS  Google Scholar 

  26. De Sandre-Giovannoli A, Bernard R, Cau P et al. (2003) Lamin A truncation in Hutchinson-Gilford progeria. Science 300: 2055

    Article  PubMed  Google Scholar 

  27. Eriksson M, Brown WT, Gordon LB et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423: 293–8

    Article  PubMed  CAS  Google Scholar 

  28. Caux F, Dubosclard E, Lascols O et al. (2003) A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J Clin Endocrinol Metab 88: 1006–113

    Article  PubMed  CAS  Google Scholar 

  29. Garg A, Subramanyam L, Agarwal AK et al. (2009) Atypical progeroid syndrome due to heterozygous missense LMNA mutations. J Clin Endocrinol Metab 94: 4971–83

    Article  PubMed  CAS  Google Scholar 

  30. Agarwal AK, Fryns JP, Auchus RJ et al. (2003) Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet 12: 1995–2001

    Article  PubMed  CAS  Google Scholar 

  31. Parker VE, Savage DB, O’Rahilly S et al. (2011) Mechanistic insights into insulin resistance in the genetic era. Diabetic Med 28: 1476–86

    Article  PubMed  CAS  Google Scholar 

  32. Le Dour C, Schneebeli S, Bakiri F et al. (2011) A homozygous mutation of prelamin-A preventing its farnesylation and maturation leads to a severe lipodystrophic phenotype: new insights into the pathogenicity of nonfarnesylated prelamin-A. J Clin Endocrinol Metab 96: E856–62

    Article  PubMed  Google Scholar 

  33. Novelli G, Muchir A, Sangiuolo F et al. (2002) Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet 71: 426–31

    Article  PubMed  CAS  Google Scholar 

  34. Worman HJ (2012) Nuclear lamins and laminopathies. J Pathol: 226: 316–25

    Article  PubMed  CAS  Google Scholar 

  35. Shackleton S, Lloyd DJ, Jackson SN et al. (2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nature Genet 24: 153–6

    Article  PubMed  CAS  Google Scholar 

  36. Béréziat V, Cervera P, Le Dour C et al. (2011) LMNA Mutations Induce a Non-Inflammatory Fibrosis and a Brown Fat-Like Dystrophy of Enlarged Cervical Adipose Tissue. Am J Pathol 179: 2445–53

    Article  Google Scholar 

  37. Vigouroux C, Magre J, Vantyghem MC et al. (2000) Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy. Diabetes 49: 1958–62

    Article  PubMed  CAS  Google Scholar 

  38. Decaudain A, Vantyghem MC, Guerci B et al. (2007) New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome. J Clin Endocrinol Metab 92: 4835–44

    Article  PubMed  CAS  Google Scholar 

  39. Young J, Morbois-Trabut L, Couzinet B et al. (2005) Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes 54: 1873–8

    Article  PubMed  CAS  Google Scholar 

  40. Rosen ED, Sarraf P, Troy AE et al. (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4: 611–7

    Article  PubMed  CAS  Google Scholar 

  41. Duan SZ, Usher MG, Mortensen RM (2009) PPARs: the vasculature, inflammation and hypertension. Curr Opin Nephrol Hypertens 18: 128–33

    Article  PubMed  CAS  Google Scholar 

  42. Jeninga EH, Gurnell M, Kalkhoven E (2009) Functional implications of genetic variation in human PPAR γ. Trends Endocrinol Metab 20: 380–7

    Article  PubMed  CAS  Google Scholar 

  43. Tan K, Kimber WA, Luan J et al. (2007) Analysis of genetic variation in Akt2/PKB-beta in severe insulin resistance, lipodystrophy, type 2 diabetes, and related metabolic phenotypes. Diabetes 56: 714–19

    Article  PubMed  CAS  Google Scholar 

  44. Hussain K, Challis B, Rocha N et al. (2011) An activating mutation of AKT2 and human hypoglycemia. Science 334: 474

    Article  PubMed  CAS  Google Scholar 

  45. Li F, Gu Y, Dong W et al. (2010) Cell death-inducing DFF45-like effector, a lipid dropletassociated protein, might be involved in the differentiation of human adipocytes. FEBS J 277: 4173–83

    Article  PubMed  CAS  Google Scholar 

  46. 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 

  47. Gandotra S, Lim K, Girousse A et al. (2011) Human Frame Shift Mutations Affecting the Carboxyl Terminus of Perilipin Increase Lipolysis by Failing to Sequester the Adipose Triglyceride Lipase (ATGL) Coactivator AB-hydrolase-containing 5 (ABHD5). J Biol Chem 286: 34998–5006

    Article  PubMed  CAS  Google Scholar 

  48. Savage DB, Semple RK, Clatworthy MR et al. (2009) Complement abnormalities in acquired lipodystrophy revisited. J Clin Endocrinol Metab 94: 10–6

    Article  PubMed  CAS  Google Scholar 

  49. Agarwal AK, Xing C, DeMartino GN et al. (2010) PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am J Hum Genet 87: 866–72

    Article  PubMed  CAS  Google Scholar 

  50. Kitamura A, Maekawa Y, Uehara H et al. (2011) A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Invest 121: 4150–60

    Article  PubMed  CAS  Google Scholar 

  51. Hegele RA, Cao H, Liu DM et al. (2006) Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet 79: 383–9

    Article  PubMed  CAS  Google Scholar 

  52. Manolopoulos KN, Karpe F, Frayn KN (2010) Gluteofemoral body fat as a determinant of metabolic health. Int J Obes 34: 949–59

    Article  CAS  Google Scholar 

  53. Caron-Debarle M, Lagathu C, Boccara F et al. (2010) HIV-associated lipodystrophy: from fat injury to premature aging. Trends Mol Med 16: 218–29

    Article  PubMed  CAS  Google Scholar 

  54. Boufassa F, Goujard C, Viard JP et al. (2012) Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naïve HIV-1-infected patients: the ANRS COPANA cohort. Antiviral Ther 17: 91–100

    Article  CAS  Google Scholar 

  55. Capeau J, Bouteloup V, Katlama C et al. (2011) Ten-year diabetes incidence in 1,046 HIV-infected patients started on a combination antiretroviral treatment: the ANRS CO8 APROCO-COPILOTE Cohort. AIDS 26: 303–14

    Article  Google Scholar 

  56. Caron M, Auclair M, Donadille B et al. (2007) Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence. Cell Death Differ 14: 1759-67

    Google Scholar 

  57. Lefèvre C, Auclair M, Boccara F et al. (2010) Premature senescence of vascular cells is induced by HIV protease inhibitors: implication of prelamin A and reversion by statin. Arterioscler Thromb Vasc Biol 30: 2611–20

    Article  PubMed  Google Scholar 

  58. Fardet L, Cabane J, Lebbe C et al. (2007) Incidence and risk factors for corticosteroidinduced lipodystrophy: a prospective study. J Am Acad Dermatol 57: 604–9

    Article  PubMed  Google Scholar 

  59. Huang-Doran I, Sleigh A, Rochford JJ et al. (2010) Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol 207: 245–55

    Article  PubMed  CAS  Google Scholar 

  60. Chong AY, Lupsa BC, Cochran EK et al. (2010) Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia 53: 27–35

    Article  PubMed  CAS  Google Scholar 

  61. Oral EA, Simha V, Ruiz E et al. (2002) Leptin-replacement therapy for lipodystrophy. N Engl J Med 346: 570–78

    Article  PubMed  CAS  Google Scholar 

  62. Arioglu E, Duncan-Morin J, Sebring N et al. (2000) Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med 133: 263–74

    PubMed  CAS  Google Scholar 

  63. Slama L, Lanoy E, Valantin MA et al. (2008) Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther 13: 67–76

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. CDR Saint-Antoine INSERM UMRS 938, Faculté de Médecine et Université Pierre et Marie Curie, Site Saint-Antoine, 27, rue Chaligny, 75571, Paris Cedex 12, France

    C. Vigouroux, V. Béréziat, M. Caron-Debarle & J. Capeau

  2. Service de biochimie et hormonologie, hôpital Tenon, AP-HP, 4 rue de la Chine, 75970, Paris Cedex 20, France

    C. Vigouroux & J. Capeau

Authors
  1. C. Vigouroux
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  2. V. Béréziat
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  3. M. Caron-Debarle
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  4. J. Capeau
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Correspondence to J. Capeau .

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Vigouroux, C., Béréziat, V., Caron-Debarle, M., Capeau, J. (2013). Syndromes lipodystrophiques génétiques et acquis. In: Physiologie et physiopathologie du tissu adipeux. Springer, Paris. https://doi.org/10.1007/978-2-8178-0332-6_25

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  • DOI: https://doi.org/10.1007/978-2-8178-0332-6_25

  • Publisher Name: Springer, Paris

  • Print ISBN: 978-2-8178-0331-9

  • Online ISBN: 978-2-8178-0332-6

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