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

  • Genetics (TM Frayling, Section Editor)
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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.

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Acknowledgments

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

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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.

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Authors and Affiliations

  1. INSERM UMR_S938, Centre de Recherche Saint-Antoine, 75012, Paris, France

    Camille Vatier, Guillaume Bidault, Nolwenn Briand, Anne-Claire Guénantin, Laurence Teyssières, Olivier Lascols, Jacqueline Capeau & Corinne Vigouroux

  2. UPMC Univ Paris 6, UMR_S938, 75012, Paris, France

    Camille Vatier, Guillaume Bidault, Nolwenn Briand, Anne-Claire Guénantin, Laurence Teyssières, Olivier Lascols, Jacqueline Capeau & Corinne Vigouroux

  3. ICAN, Institute of Cardiometabolism and Nutrition, Paris, France

    Camille Vatier, Guillaume Bidault, Nolwenn Briand, Anne-Claire Guénantin, Laurence Teyssières, Olivier Lascols, Jacqueline Capeau & Corinne Vigouroux

  4. AP-HP, Hôpital Pitié-Salpêtrière, Service de Nutrition, 75013, Paris, France

    Camille Vatier

  5. AP-HP, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, 75012, Paris, France

    Olivier Lascols

  6. AP-HP, Hôpital Tenon, Service de Biochimie et Hormonologie, 75020, Paris, France

    Jacqueline Capeau & Corinne Vigouroux

  7. Faculté de Médecine Pierre et Marie Curie, site Saint-Antoine, UMR_S938, 27 rue Chaligny, 75012, Paris, France

    Corinne Vigouroux

Authors
  1. Camille Vatier
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  2. Guillaume Bidault
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  3. Nolwenn Briand
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  4. Anne-Claire Guénantin
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  5. Laurence Teyssières
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  6. Olivier Lascols
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  7. Jacqueline Capeau
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  8. Corinne Vigouroux
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Corresponding author

Correspondence to Corinne Vigouroux.

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Vatier, C., Bidault, G., Briand, N. et al. What the Genetics of Lipodystrophy Can Teach Us About Insulin Resistance and Diabetes. Curr Diab Rep 13, 757–767 (2013). https://doi.org/10.1007/s11892-013-0431-7

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  • DOI: https://doi.org/10.1007/s11892-013-0431-7

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