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)

Abstract

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.

Keywords

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 

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Copyright information

© 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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