title: LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations.
abstract: Mutations in the LMNA gene, encoding the nuclear intermediate filaments the A-type lamins, result in a wide variety of diseases known as laminopathies. Some of them, such as familial partial lipodystrophy of Dunnigan and metabolic laminopathies, are characterized by lipodystrophic syndromes with altered fat distribution and severe metabolic alterations with insulin resistance and dyslipidaemia. Metabolic disturbances could be due either to the inability of adipose tissue to adequately store triacylglycerols or to other cellular alterations linked to A-type lamin mutations. Indeed, abnormal prelamin A accumulation and farnesylation, which are clearly involved in laminopathic premature aging syndromes, could play important roles in lipodystrophies. In addition, gene expression alterations, and signalling abnormalities affecting SREBP1 (sterol-regulatory-element-binding protein 1) and MAPK (mitogen-activated protein kinase) pathways, could participate in the pathophysiological mechanisms leading to LMNA (lamin A/C)-linked metabolic alterations and lipodystrophies. In the present review, we describe the clinical phenotype of LMNA-linked lipodystrophies and discuss the current physiological and biochemical hypotheses regarding the pathophysiology of these diseases.
authors: UMPC Université Paris 6, UMR S938, F-75005 Paris, France.
authors: Guillaume
authors: G
authors: Bidault
authors: Camille
authors: C
authors: Vatier
authors: Jacqueline
authors: J
authors: Capeau
authors: Corinne
authors: C
authors: Vigouroux
authors: Véronique
authors: V
authors: Béréziat
mesh_terms: D050154:Adiposity / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D034904:Lamin Type A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008060:Lipodystrophy / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D009687:Nuclear Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A