University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
N Engl J Med. 2011 Feb 24;364(8):740-8. doi: 10.1056/NEJMoa1007487.
Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. We identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue.
脂肪甘油三酯脂酶是最丰富的脂肪细胞特异性蛋白，它覆盖在脂肪滴的表面，对于脂肪滴内脂质的最佳摄取和释放是必需的。我们在三个家族性部分脂肪营养不良、严重血脂异常和胰岛素抵抗性糖尿病患者中发现了脂肪甘油三酯脂酶基因（PLIN1）的两个杂合移码突变。患者的皮下脂肪表现为比正常小的脂肪细胞、巨噬细胞浸润和纤维化。与野生型脂肪甘油三酯脂酶不同，当在脂肪前体细胞中异源表达时，突变蛋白形式不能增加甘油三酯的积累。这些发现定义了一种新的显性遗传性脂肪营养不良形式，并强调了脂肪组织中脂肪滴形成的主要缺陷的严重代谢后果。
