INSERM UMR_S938, Centre de Recherche Saint-Antoine, 75012, Paris, France.
Curr Diab Rep. 2013 Dec;13(6):757-67. doi: 10.1007/s11892-013-0431-7.
Genetic lipodystrophic syndromes are rare diseases characterized by generalized or partial fat atrophy (lipoatrophy) associated with severe metabolic complications such as insulin resistance (IR), diabetes, dyslipidemia, nonalcoholic fatty liver disease, and ovarian hyperandrogenism. During the last 15 years, mutations in several genes have been shown to be responsible for monogenic forms of lipodystrophic syndromes, of autosomal dominant or recessive transmission. Although the molecular basis of lipodystrophies is heterogeneous, most mutated genes lead to impaired adipogenesis, adipocyte lipid storage, and/or formation or maintenance of the adipocyte lipid droplet (LD), showing that primary alterations of adipose tissue (AT) can result in severe systemic metabolic and endocrine consequences. The reduced expandability of AT alters its ability to buffer excess caloric intake, leading to ectopic lipid storage that impairs insulin signaling and other cellular functions ("lipotoxicity"). Genetic studies have also pointed out the close relationships between ageing, inflammatory processes, lipodystrophy, and IR.
遗传性脂肪营养不良综合征是一种罕见疾病，其特征为全身性或局部脂肪萎缩（脂肪减少症），并伴有严重的代谢并发症，如胰岛素抵抗（IR）、糖尿病、血脂异常、非酒精性脂肪肝和卵巢高雄激素血症。在过去的 15 年中，已经发现几种基因突变可导致常染色体显性或隐性遗传的单基因脂肪营养不良综合征。尽管脂肪营养不良的分子基础存在异质性，但大多数突变基因导致脂肪生成、脂肪细胞脂质储存受损和/或脂肪细胞脂质滴（LD）的形成或维持受损，这表明脂肪组织（AT）的主要改变可导致严重的全身代谢和内分泌后果。AT 的可扩展性降低会改变其缓冲多余热量摄入的能力，导致异位脂质储存，从而损害胰岛素信号和其他细胞功能（“脂毒性”）。遗传研究还指出了衰老、炎症过程、脂肪营养不良和 IR 之间的密切关系。
