Guénantin A C, Briand N, Bidault G, Afonso P, Béréziat V, Vatier C, Lascols O, Caron-Debarle M, Capeau J, Vigouroux C
INSERM UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.
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.
Semin Cell Dev Biol. 2014 May;29:148-57. doi: 10.1016/j.semcdb.2013.12.015. Epub 2013 Dec 30.
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.
在内核膜下方构成核纤层网络的核膜蛋白的几种改变（核纤层蛋白A/C突变、前体核纤层蛋白A成熟改变、核纤层蛋白B突变或失调）已被证明与人类脂肪营养不良综合征有关或导致该综合征。脂肪营养不良综合征是罕见的异质性疾病，可分为遗传性或获得性，其特征为全身性或部分性脂肪萎缩，并伴有包括胰岛素抵抗性糖尿病、血脂异常和非酒精性脂肪肝病在内的代谢并发症。不同类型脂肪营养不良的分子遗传学的最新进展通常指向原发性脂肪细胞改变，导致脂肪生成受损和/或脂肪细胞脂质小滴失调。然而，将核膜异常与脂肪营养不良联系起来的精确机制在很大程度上仍然未知。与核膜相关的脂肪营养不良的表型范围从典型的邓尼根型家族性部分脂肪营养不良（FPLD2），这是由于核纤层蛋白A/C第482位精氨酸的杂合性替代，到可合并脂肪营养不良、代谢并发症、肌肉或心脏改变和/或加速衰老迹象的复杂疾病。在本综述中，我们介绍了与核膜相关的脂肪营养不良的临床、组织和细胞特征，以及它们假设的病理生理机制。
