Current Diabetes Reports

, Volume 13, Issue 6, pp 757–767 | Cite as

What the Genetics of Lipodystrophy Can Teach Us About Insulin Resistance and Diabetes

  • Camille Vatier
  • Guillaume Bidault
  • Nolwenn Briand
  • Anne-Claire Guénantin
  • Laurence Teyssières
  • Olivier Lascols
  • Jacqueline Capeau
  • Corinne Vigouroux
Genetics (TM Frayling, Section Editor)


Genetic lipodystrophic syndromes are rare diseases characterized by generalized or partial fat atrophy (lipoatrophy) associated with severe metabolic complications such as insulin resistance (IR), diabetes, dyslipidemia, nonalcoholic fatty liver disease, and ovarian hyperandrogenism. During the last 15 years, mutations in several genes have been shown to be responsible for monogenic forms of lipodystrophic syndromes, of autosomal dominant or recessive transmission. Although the molecular basis of lipodystrophies is heterogeneous, most mutated genes lead to impaired adipogenesis, adipocyte lipid storage, and/or formation or maintenance of the adipocyte lipid droplet (LD), showing that primary alterations of adipose tissue (AT) can result in severe systemic metabolic and endocrine consequences. The reduced expandability of AT alters its ability to buffer excess caloric intake, leading to ectopic lipid storage that impairs insulin signaling and other cellular functions (“lipotoxicity”). Genetic studies have also pointed out the close relationships between ageing, inflammatory processes, lipodystrophy, and IR.


Adipose tissue Lipodystrophy Lipid droplets Adipogenesis Insulin resistance Diabetes Dyslipidemia Liver steatosis Polycystic ovary syndrome Ageing Genetics Seipin AGPAT2 A-type lamins PPARγ Perilipin Caveolin 1 Cavin 1 Caveolae CIDEC Akt2 PSMB8 Progeria ZMPSTE24 Genetics 



The researches of the authors are supported by Institut de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), and Agence Nationale de la Recherche (program “Investments for the Future”, Institute of Cardiometabolism and Nutrition [ICAN]; grant no. ANR-10-IAHU).

C. Vatier is the recipient of a PhD grant from the Conseil Régional d’Ile de France (Cardiovasculaire-Obésité-Diabète Domaine d’Intérêt Majeur), G. Bidault. of a PhD grant from the Fondation pour la Recherche Médicale, N. Briand of post-doctoral grant from Région Ile-de-France (DIM Biotherapies), A-C. Guénantin of a post-doctoral grant from Institute of Cardiometabolism and Nutrition (Innovative projects 2012) and L. Teyssières of a master grant from Agence Régionale de Santé Limousin.

Compliance with Ethics Guidelines

Conflict of Interest

Camille Vatier has been on the Advisory board on lipodystrophy and leptin for Astra-Zeneca; has received the SFE 2012 Oral communication award from Novartis; has received honoraria from Sanofi; has received payment for manuscript preparation from Elsevier Masson; and has received travel/accommodations expenses covered or reimbursed for meetings from Novo-Nordisk, Servier, and Lilly.

Guillaume Bidault declares that he has no conflict of interest. Nolwenn Briand declares that she has no conflict of interest. Anne-Claire Guénantin declares that she has no conflict of interest. Laurence Teyssières declares that she has no conflict of interest. Olivier Lascols declares that he has no conflict of interest. Jacqueline Capeau declares that she has no conflict of interest. Corinne Vigouroux has been on the Advisory board on lipodystrophy and leptin for Astra-Zeneca; and has received travel/accommodations expenses covered or reimbursed for meetings from Boehringer-Ingelheim, Novo-Nordisk, Edimark Santé, and Vitalaire.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Garg A. Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab. 2011;96:3313–25.PubMedCrossRefGoogle Scholar
  2. 2.
    Vigouroux C, Caron-Debarle M, Le Dour C, Magré J, Capeau J. Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity. Int J Biochem Cell Biol. 2011;43:862–76.PubMedCrossRefGoogle Scholar
  3. 3.
    Barroso I, Gurnell M, Crowley VE, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402:880–3.PubMedGoogle Scholar
  4. 4.
    Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet. 2000;9:109–12.PubMedCrossRefGoogle Scholar
  5. 5.
    Shackleton S, Lloyd DJ, Jackson SN, et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000;24:153–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Magré J, Delépine M, Khallouf E, et al. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nature Genet. 2001;28:365–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Agarwal AK, Arioglu E, De Almeida S, et al. AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat Genet. 2002;31:21–3.PubMedCrossRefGoogle Scholar
  8. 8.
    George S, Rochford JJ, Wolfrum C, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science. 2004;304:1325–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Kim C, Delépine M, Boutet E, et al. Association of a homozygous nonsense Caveolin-1 mutation with Berardinelli-Seip Congenital Lipodystrophy. J Clin Endocrinol Metab. 2008;93:1129–34.PubMedCrossRefGoogle Scholar
  10. 10.
    Rubio-Cabezas O, Puri V, Murano I, et al. Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Mol Med. 2009;1:280–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Hayashi YK, Matsuda C, Ogawa M, et al. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest. 2009;119:2623–33.PubMedCrossRefGoogle Scholar
  12. 12.
    •• Gandotra S, Le Dour C, Bottomley W, et al. Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med. 2011;364:740–8. Each of these studies (references 3–12) identified genes involved in lipodystrophic syndromes, underlying the importance of a primary defect in adipose tissue for metabolism at the systemic level.PubMedCrossRefGoogle Scholar
  13. 13.
    Novelli G, Muchir A, Sangiuolo F, et al. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet. 2002;71:426–31.PubMedCrossRefGoogle Scholar
  14. 14.
    De Sandre-Giovannoli A, Bernard R, Cau P, et al. Lamin A truncation in Hutchinson-Gilford progeria. Science. 2003;300:2055.PubMedCrossRefGoogle Scholar
  15. 15.
    Eriksson M, Brown WT, Gordon LB, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423:293–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Agarwal AK, Fryns JP, Auchus RJ, Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet. 2003;12:1995–2001.PubMedCrossRefGoogle Scholar
  17. 17.
    Caron M, Auclair M, Donadille B, et al. 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. 2007;14:1759–67.PubMedCrossRefGoogle Scholar
  18. 18.
    •• Agarwal AK, Xing C, DeMartino GN, et al. PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am J Hum Genet. 2010;87:866–72. This work reported the identification of PSMB8 as the gene involved in JMP syndrome, showing that autoinflammation can lead to lipodystrophy.PubMedCrossRefGoogle Scholar
  19. 19.
    Kitamura A, Maekawa Y, Uehara H, et al. A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Invest. 2011;121:4150–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Ailhaud G. Adipose tissue as an endocrine organ. Int J Obes Relat Metab Disord. 2000;24 Suppl 2:S1–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Bastard JP, Fève B. The secretory face of the adipose cell: a tribute to two queens, leptin and adiponectin. Biochimie. 2012;94:2063–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Goossens GH, Blaak EE, van Baak MA. Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders. Obes Rev. 2003;4:43–55.PubMedCrossRefGoogle Scholar
  23. 23.
    Caspar-Bauguil S, Cousin B, Bour S, et al. Adipose tissue lymphocytes: types and roles. J Physiol Biochem. 2009;65:423–36.PubMedCrossRefGoogle Scholar
  24. 24.
    Dirat B, Bochet L, Dabek M, et al. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 2011;71:2455–65.PubMedCrossRefGoogle Scholar
  25. 25.
    Shimomura I, Hammer RE, Richardson JA, et al. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998;12:3182–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Moitra J, Mason MM, Olive M, et al. Life without white fat: a transgenic mouse. Genes Dev. 1998;12:3168–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Gavrilova O, Marcus-Samuels B, Graham D, et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest. 2000;105:271–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Colombo C, Cutson JJ, Yamauchi T, et al. Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy. Diabetes. 2002;51:2727–33.PubMedCrossRefGoogle Scholar
  29. 29.
    Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350:1220–34.PubMedCrossRefGoogle Scholar
  31. 31.
    Seip M, Trygstad O. Generalized lipodystrophy, congenital and acquired (lipoatrophy). Acta Paediatr Suppl. 1996;413:2–28.PubMedCrossRefGoogle Scholar
  32. 32.
    Dunnigan MG, Cochrane MA, Kelly A, Scott JW. Familial lipoatrophic diabetes with dominant transmission. A new syndrome. Q J Med. 1974;43:33–48.PubMedGoogle Scholar
  33. 33.
    Garg A, Peshock RM, Fleckenstein JL. Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab. 1999;84:170–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Vantyghem MC, Vincent-Desplanques D, Defrance-Faivre F, et al. Fertility and obstetrical complications in women with LMNA-related familial partial lipodystrophy. J Clin Endocrinol Metab. 2008;96:2223–9.CrossRefGoogle Scholar
  35. 35.
    Haque WA, Shimomura I, Matsuzawa Y, Garg A. Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab. 2002;87:2395–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Antuna-Puente B, Boutet E, Vigouroux C, et al. Higher adiponectin levels in patients with Berardinelli-Seip congenital lipodystrophy due to seipin compared with 1-acylglycerol-3-phosphate-o-acyltransferase-2 deficiency. J Clin Endocrinol Metab. 2010;95:1463–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Valerio CM, Godoy-Matos A, Moreira RO, et al. Dual-energy X-ray absorptiometry study of body composition in patients with lipodystrophy. Diabetes Care. 2007;30:1857–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Abate N, Burns D, Peshock RM, Garg A, Grundy SM. Estimation of adipose tissue mass by magnetic resonance imaging: validation against dissection in human cadavers. J Lipid Res. 1994;35:1490–6.PubMedGoogle Scholar
  39. 39.
    Brunzell JD, Shankle SW, Bethune JE. Congenital generalized lipodystrophy accompanied by cystic angiomatosis. Ann Intern Med. 1968;69:501–16.PubMedCrossRefGoogle Scholar
  40. 40.
    Decaudain A, Vantyghem MC, Guerci B, et al. New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome. J Clin Endocrinol Metab. 2007;92:4835–44.PubMedCrossRefGoogle Scholar
  41. 41.
    Semple RK, Savage DB, Cochran EK, Gorden P, O’Rahilly S. Genetic syndromes of severe insulin resistance. Endocr Rev. 2011;32:498–514.PubMedCrossRefGoogle Scholar
  42. 42.
    Semple RK, Sleigh A, Murgatroyd PR, et al. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest. 2009;119:315–22.PubMedGoogle Scholar
  43. 43.
    Thauvin-Robinet C, Auclair M, Duplomb L, et al. Mutations in PIK3R1 cause syndromic insulin resistance with lipoatrophy. Am J Hum Genet. 2013;93:141–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Van Maldergem L, Magré J, Gedde-Dahl Jr T, et al. Genotype-phenotype relationships in berardinelli-seip congenital lipodystrophy. J Med Genet. 2002;39:722–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Simha V, Garg A. 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. 2003;88:5433–7.PubMedCrossRefGoogle Scholar
  46. 46.
    • Agarwal AK. Lysophospholipid acyltransferases: 1-acylglycerol-3-phosphate O-acyltransferases. From discovery to disease. Curr Opin Lipidol. 2012;23:290–302. A comprehensive review about the role of AGPAT isoforms.PubMedCrossRefGoogle Scholar
  47. 47.
    Subauste AR, Das AK, Li X, et al. Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations. Diabetes. 2012;61:2922–31.PubMedCrossRefGoogle Scholar
  48. 48.
    • Cartwright BR, Goodman JM. Seipin: from human disease to molecular mechanism. J Lipid Res. 2012;53:1042–55. A recent complete review on the role of seipin, in particular in lipid droplet assembly and maintenance and in adipocyte differentiation.PubMedCrossRefGoogle Scholar
  49. 49.
    Szymanski KM, Binns D, Bartz R, et al. The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc Natl Acad Sci U S A. 2007;104:20890–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Boutet E, El Mourabit H, Prot M, et al. Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy. Biochimie. 2009;91:796–803.PubMedCrossRefGoogle Scholar
  51. 51.
    • Yang H, Galea A, Sytnyk V, Crossley M. Controlling the size of lipid droplets: lipid and protein factors. Curr Opin Cell Biol. 2012;24:509–16. A comprehensive review about the structure of lipid droplets and the mechanisms involved in their assembly and growth.PubMedCrossRefGoogle Scholar
  52. 52.
    Ito D, Suzuki N. Seipinopathy: a novel endoplasmic reticulum stress-associated disease. Brain. 2009;132:8–15.PubMedCrossRefGoogle Scholar
  53. 53.
    Holtta-Vuori M, Salo VT, Ohsaki Y, Suster ML, Ikonen E. Alleviation of seipinopathy-related ER stress by triglyceride storage. Hum Mol Genet. 2013;22:1157–66.PubMedCrossRefGoogle Scholar
  54. 54.
    Cao H, Alston L, Ruschman J, Hegele RA. Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. Lipids Health Dis. 2008;7:3.PubMedCrossRefGoogle Scholar
  55. 55.
    Ostermeyer AG, Paci JM, Zeng Y, et al. Accumulation of caveolin in the endoplasmic reticulum redirects the protein to lipid storage droplets. J Cell Biol. 2001;152:1071–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Pol A, Luetterforst R, Lindsay M, et al. A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. J Cell Biol. 2001;152:1057–70.PubMedCrossRefGoogle Scholar
  57. 57.
    • Le Lay S, Briand N, Blouin CM, et al. The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes. Autophagy. 2010;6:754–63. Autophagy, a new pathway involved in lipodystrophy in caveolin-1 deficient mice.PubMedCrossRefGoogle Scholar
  58. 58.
    Blouin CM, Le Lay S, Eberl A, et al. Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects. J Lipid Res. 2010;51:945–56.PubMedCrossRefGoogle Scholar
  59. 59.
    Rajab A, Straub V, McCann LJ, et al. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet. 2010;6:e1000874.PubMedCrossRefGoogle Scholar
  60. 60.
    Hill MM, Bastiani M, Luetterforst R, et al. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell. 2008;132:113–24.PubMedCrossRefGoogle Scholar
  61. 61.
    Le Dour C, Schneebeli S, Bakiri F, et al. 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. 2011;96:E856–62.PubMedCrossRefGoogle Scholar
  62. 62.
    Wiltshire KM, Hegele RA, Innes AM, Brownell AK. Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy. Neuromuscul Disord. 2013;23:265–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Worman HJ. Nuclear lamins and laminopathies. J Pathol. 2012;226:316–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Burke B, Stewart CL. The nuclear lamins: flexibility in function. Nat Rev Mol Cell Biol. 2013;14:13–24.PubMedCrossRefGoogle Scholar
  65. 65.
    Vigouroux C, Magré J, Vantyghem MC, et al. 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. 2000;49:1958–62.PubMedCrossRefGoogle Scholar
  66. 66.
    Araújo-Vilar D, Loidi L, Domínguez F, Cabezas-Cerrato J. Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A/C R482W mutation. Horm Metab Res. 2003;35:29–35.PubMedCrossRefGoogle Scholar
  67. 67.
    • Béréziat V, Cervera P, Le Dour C, et al. LMNA mutations induce a non-inflammatory fibrosis and a brown fat-like dystrophy of enlarged cervical adipose tissue. Am J Pathol. 2011;179:2443–53. This work reported that accumulated adipose tissue in familial partial lipodystrophy is dystrophic, showing fibrosis and an altered differentiation pattern with brown fat-like adipocytes.PubMedCrossRefGoogle Scholar
  68. 68.
    Mory PB, Crispim F, Freire MB, et al. Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations. Eur J Endocrinol. 2012;167:423–31.PubMedCrossRefGoogle Scholar
  69. 69.
    Caux F, Dubosclard E, Lascols O, et al. 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. 2003;88:1006–13.PubMedCrossRefGoogle Scholar
  70. 70.
    Garg A, Subramanyam L, Agarwal AK, et al. Atypical progeroid syndrome due to heterozygous missense LMNA mutations. J Clin Endocrinol Metab. 2009;94:4971–83.PubMedCrossRefGoogle Scholar
  71. 71.
    Capanni C, Mattioli E, Columbaro M, et al. Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum Mol Genet. 2005;14:1489–502.PubMedCrossRefGoogle Scholar
  72. 72.
    •• Liu GH, Barkho BZ, Ruiz S, et al. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature. 2011;472:221–5. These 2 studies highlighted the role of progerin (prelamin A mutated in Hutchinson-Gilford progeria) in ageing-associated cell phenotypes during differentiation and showed that iPSC are a model for studying the pathogenesis of laminopathies.PubMedCrossRefGoogle Scholar
  73. 73.
    •• Zhang J, Lian Q, Zhu G, et al. A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell. 2011;8:31–45. These 2 studies highlighted the role of progerin (prelamin A mutated in Hutchinson-Gilford progeria) in ageing-associated cell phenotypes during differentiation and showed that iPSC are a model for studying the pathogenesis of laminopathies.PubMedCrossRefGoogle Scholar
  74. 74.
    Scaffidi P, Misteli T. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol. 2008;10:452–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Pekovic V, Hutchison CJ. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. J Anat. 2008;213:5–25.PubMedCrossRefGoogle Scholar
  76. 76.
    Naetar N, Foisner R. Lamin complexes in the nuclear interior control progenitor cell proliferation and tissue homeostasis. Cell Cycle. 2009;8:1488–93.PubMedCrossRefGoogle Scholar
  77. 77.
    Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem. 2008;77:289–312.PubMedCrossRefGoogle Scholar
  78. 78.
    Jeninga EH, Gurnell M, Kalkhoven E. Functional implications of genetic variation in human PPARgamma. Trends Endocrinol Metab. 2009;20:380–7.PubMedCrossRefGoogle Scholar
  79. 79.
    • Auclair M, Vigouroux C, Boccara F, et al. Peroxisome proliferator-activated receptor-gamma mutations responsible for lipodystrophy with severe hypertension activate the cellular renin-angiotensin system. Arterioscler Thrombos Vasc Biol. 2013;33:829–38. A translational study of peroxisome proliferator-activated receptor γ translational study of peroxisome proliferator-activated rsupporting a role for PPARγ as a regulator of blood pressure through its ability to modulate the cellular renin-angiotensin system.CrossRefGoogle Scholar
  80. 80.
    Li F, Gu Y, Dong W, et al. Cell death-inducing DFF45-like effector, a lipid droplet-associated protein, might be involved in the differentiation of human adipocytes. FEBS J. 2010;277:4173–83.PubMedCrossRefGoogle Scholar
  81. 81.
    Gandotra S, Lim K, Girousse A, et al. 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. 2011;286:34998–5006.PubMedCrossRefGoogle Scholar
  82. 82.
    Hegele RA, Cao H, Liu DM, et al. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet. 2006;79:383–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Gao J, Li Y, Fu X, Luo X. A Chinese patient with acquired partial lipodystrophy caused by a novel mutation with LMNB2 gene. J Pediatr Endocrinol Metab. 2012;25:375–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Coffinier C, Hudon SE, Farber EA, et al. HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells. Proc Natl Acad Sci U S A. 2007;104:13432–7.PubMedCrossRefGoogle Scholar
  85. 85.
    •• Gordon LB, Kleinman ME, Miller DT, et al. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2012;109:16666–71. Results from the first clinical trial with farnesyl-transferase inhibitor in Hutchinson-Gilford progeria syndrome, showing the improvement of vascular stiffness and bone structure.PubMedCrossRefGoogle Scholar
  86. 86.
    Donadille B, D’Anella P, Auclair M, et al. Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome. Orphanet J Rare Dis. 2013;8:106.PubMedCrossRefGoogle Scholar
  87. 87.
    Weedon MN, Ellard S, Prindle MJ, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat Genet. 2013; [In press].Google Scholar
  88. 88.
    Dahl PR, Zalla MJ, Winkelmann RK. Localized involutional lipoatrophy: a clinicopathologic study of 16 patients. J Am Acad Dermatol. 1996;35:523–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes. 2010;34:949–59.CrossRefGoogle Scholar
  90. 90.
    Virtue S, Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome–an allostatic perspective. Biochim Biophys Acta. 1801;2010:338–49.Google Scholar
  91. 91.
    Wilson DE, Chan IF, Stevenson KB, Horton SC, Schipke C. Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids in acquired total lipodystrophy: effects on hyperlipoproteinemia and endogenous insulin resistance. J Clin Endocrinol Metab. 1983;57:517–23.PubMedCrossRefGoogle Scholar
  92. 92.
    Agarwal AK, Garg A. Genetic basis of lipodystrophies and management of metabolic complications. Annu Rev Med. 2006;57:297–311.PubMedCrossRefGoogle Scholar
  93. 93.
    Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346:570–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Oral EA, Ruiz E, Andewelt A, et al. Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy. J Clin Endocrinol Metab. 2002;87:3110–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Javor ED, Cochran EK, Musso C, et al. Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes. 2005;54:1994–2002.PubMedCrossRefGoogle Scholar
  96. 96.
    Ebihara K, Kusakabe T, Hirata M, et al. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2007;92:532–41.PubMedCrossRefGoogle Scholar
  97. 97.
    Yu X, McCorkle S, Wang M, et al. Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia. 2004;47:2012–21.PubMedCrossRefGoogle Scholar
  98. 98.
    Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941–6.PubMedCrossRefGoogle Scholar
  99. 99.
    Calderoni DR, Ramos TM, de Castro JR, Kharmandayan P. Surgical management of phenotypic alterations related to the Dunnigan variety of familial partial lipodystrophy. J Plast Reconstr Aesthet Surg. 2011;64:1248–50.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Camille Vatier
    • 1
    • 2
    • 3
    • 4
  • Guillaume Bidault
    • 1
    • 2
    • 3
  • Nolwenn Briand
    • 1
    • 2
    • 3
  • Anne-Claire Guénantin
    • 1
    • 2
    • 3
  • Laurence Teyssières
    • 1
    • 2
    • 3
  • Olivier Lascols
    • 1
    • 2
    • 3
    • 5
  • Jacqueline Capeau
    • 1
    • 2
    • 3
    • 6
  • Corinne Vigouroux
    • 1
    • 2
    • 3
    • 6
    • 7
  1. 1.INSERM UMR_S938Centre de Recherche Saint-AntoineParisFrance
  2. 2.UPMC Univ Paris 6, UMR_S938ParisFrance
  3. 3.ICAN, Institute of Cardiometabolism and NutritionParisFrance
  4. 4.AP-HP, Hôpital Pitié-Salpêtrière, Service de NutritionParisFrance
  5. 5.AP-HP, Hôpital Saint-AntoineLaboratoire Commun de Biologie et Génétique MoléculairesParisFrance
  6. 6.AP-HP, Hôpital TenonService de Biochimie et HormonologieParisFrance
  7. 7.Faculté de Médecine Pierre et Marie Curie, site Saint-Antoine, UMR_S938ParisFrance

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