title: Nuclear envelope-related lipodystrophies.
abstract: Several alterations in nuclear envelope proteins building up the lamina meshwork beneath the inner nuclear membrane (mutations in lamins A/C, alterations of prelamin-A maturation, lamin B mutations or deregulation) have been shown to be responsible for or associated to human lipodystrophic syndromes. Lipodystrophic syndromes are rare and heterogeneous diseases, either genetic or acquired, characterized by generalized or partial fat atrophy associated with metabolic complications comprising insulin-resistant diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Recent advances in the molecular genetics of different types of lipodystrophies generally pointed to primary adipocyte alterations leading to impaired adipogenesis and/or deregulation of the adipocyte lipid droplet. However, the precise mechanisms linking nuclear envelope abnormalities to lipodystrophies remain largely unknown. The phenotype of nuclear envelope-linked lipodystrophies ranges from the typical familial partial lipodystrophy of the Dunnigan type (FPLD2), due to heterozygous substitutions of the 482nd arginine of lamins A/C, to complex diseases that can combine lipodystrophy, metabolic complications, muscular or cardiac alterations and/or signs of accelerated aging. In this review we present the clinical, tissular and cellular characteristics of the nuclear envelope-linked lipodystrophies, as well as their hypothetical pathophysiological mechanisms.
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France. Electronic address: anne.claire.guenantin@inserm.fr.
authors.forename: A C
authors.initials: AC
authors.lastname: Guénantin
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France. Electronic address: nolwenn.briand@inserm.fr.
authors.forename: N
authors.initials: N
authors.lastname: Briand
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France. Electronic address: guillaume.bidault@inserm.fr.
authors.forename: G
authors.initials: G
authors.lastname: Bidault
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France. Electronic address: pauline.afonso@inserm.fr.
authors.forename: P
authors.initials: P
authors.lastname: Afonso
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France. Electronic address: veronique.bereziat@inserm.fr.
authors.forename: V
authors.initials: V
authors.lastname: Béréziat
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France. Electronic address: camille.vatier@inserm.fr.
authors.forename: C
authors.initials: C
authors.lastname: Vatier
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France; AP-HP, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, F-75012 Paris, France. Electronic address: olivier.lascols@inserm.fr.
authors.forename: O
authors.initials: O
authors.lastname: Lascols
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France. Electronic address: martine.debarle@inserm.fr.
authors.forename: M
authors.initials: M
authors.lastname: Caron-Debarle
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France; AP-HP, Hôpital Tenon, Service de Biochimie et Hormonologie, F-75020 Paris, France. Electronic address: jacqueline.capeau@inserm.fr.
authors.forename: J
authors.initials: J
authors.lastname: Capeau
authors.affiliation: INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, F-75005 Paris, France; AP-HP, Hôpital Tenon, Service de Biochimie et Hormonologie, F-75020 Paris, France. Electronic address: corinne.vigouroux@inserm.fr.
authors.forename: C
authors.initials: C
authors.lastname: Vigouroux
mesh_terms: D017667:Adipocytes / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D019588:Aging, Premature / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D050171:Dyslipidemias / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D034904:Lamin Type A / Q000235:genetics*; D034921:Lamin Type B / Q000235:genetics*; D050356:Lipid Metabolism; D008060:Lipodystrophy / Q000235:genetics*; D051379:Mice; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics; D009685:Nuclear Envelope / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D034921:Lamin Type B; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A
keywords: A-type-lamins; Adipocyte; Differentiation; Insulin resistance; Lipodystrophy; Senescence