UMPC Université Paris 6, UMR S938, F-75005 Paris, France.
Biochem Soc Trans. 2011 Dec;39(6):1752-7. doi: 10.1042/BST20110675.
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.
LMNA 基因突变导致核中间丝 A 型层粘连蛋白的编码，导致了多种被称为层粘连蛋白病的疾病。其中一些疾病，如家族性部分脂肪营养不良的 Dunnigan 和代谢性层粘连蛋白病，其特征是脂肪分布改变的脂肪营养不良综合征和严重的代谢改变，伴有胰岛素抵抗和血脂异常。代谢紊乱可能是由于脂肪组织无法充分储存三酰甘油，也可能是与 A 型层粘连蛋白突变相关的其他细胞改变所致。事实上，异常的前层粘连蛋白积累和法呢基化，这显然与层粘连蛋白病性早老综合征有关，可能在脂肪营养不良中发挥重要作用。此外，影响 SREBP1（固醇调节元件结合蛋白 1）和 MAPK（丝裂原活化蛋白激酶）途径的基因表达改变和信号异常，可能参与导致与 LMNA（核纤层蛋白 A/C）相关的代谢改变和脂肪营养不良的病理生理机制。在本综述中，我们描述了与 LMNA 相关的脂肪营养不良的临床表型，并讨论了目前关于这些疾病病理生理学的生理和生化假设。
