title: [Genetics of congenital lipodystrophies].
abstract: Congenital lipodystrophies are heterogeneous genetic diseases, leading to the loss of adipose tissue. This loss of adipose tissue can be generalized or partial, thus defining different phenotypes. These lipodystrophies have a major metabolic impact, secondary to lipotoxicity. This lipotoxicity is responsible for insulin resistance, dyslipidemia and hepatic steatosis. The severity of the metabolic impact correlates with the severity of the loss of adipose tissue. Mutations in 15 predisposition genes are currently described; BSCL2 and AGPT2 genes are the major genes in the generalized forms. On the contrary, LMNA and PPARG gene mutations are recovered in partial lipodystrophies forms. These different genes encode for proteins involved in adipocyte physiology, altering adipocyte differentiation, triglycerides synthesis and lysis or playing a major role in the lipid droplet formation. Congenital lipodystrophies treatment is based on the management of metabolic comorbidities but recombinant leptin therapy appears to have promising results. These different points have been recently discussed during the 2015 Endocrine Society Congress, notably by S. O'Rahilly and are highlighted in this review.
authors.affiliation: Service d'Endocrinologie, Nutrition et Maladies Métaboliques, CHU Larrey, 24 Chemin de Pouvourville, TSA 30030, 31059 Toulouse, France. Electronic address: buffet.a@chu-toulouse.fr.
authors.forename: A
authors.initials: A
authors.lastname: Buffet
authors.affiliation: INSERM U1185, Faculté de Médecine Paris Sud, F94276 Le Kremlin Bicêtre, France.
authors.forename: M
authors.initials: M
authors.lastname: Lombes
authors.affiliation: Service d'Endocrinologie, Nutrition et Maladies Métaboliques, CHU Larrey, 24 Chemin de Pouvourville, TSA 30030, 31059 Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Caron
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000473:pathology; D000293:Adolescent; D000328:Adult; D042702:Angiopoietin-2 / Q000235:genetics; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D020738:Leptin / Q000627:therapeutic use; D008060:Lipodystrophy / Q000151:congenital* / Q000235:genetics* / Q000628:therapy; D052497:Lipodystrophy, Congenital Generalized / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D047495:PPAR gamma / Q000235:genetics; D011994:Recombinant Proteins
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; C494847:LMNA protein, human; D034904:Lamin Type A; D020738:Leptin; D047495:PPAR gamma; D011994:Recombinant Proteins
keywords: Generalized lipodystrophies; Genetics; Génétique; Lipodystrophies généralisées; Lipodystrophies partielles; Lipotoxicity; Lipotoxicité; Partial lipodystrophies; SHORT syndrome; Syndrome de SHORT