英国剑桥大学研究人员最新发现一种罕见的遗传疾病，患者的围脂滴蛋白基因变异会导致其脂肪细胞功能受到影响，从而使其身体脂肪含量均匀降低，“瘦身”效果明显。
人体许多细胞中都会存储少量脂肪，而绝大多数脂肪则存储于白色脂肪细胞中：该细胞90%的空间都被脂质滴所占据。剑桥大学的最新一项研究发现，脂肪细胞中一种围脂滴蛋白基因（PLIN1基因）的两个结构移位突变，会导致脂肪细胞脂质存储功能错乱，使患者体内脂肪含量降低。实验发现，有此基因变异的实验鼠有时甚至无法生产围脂滴蛋白。与通常的脂肪代谢障碍不同，该基因变异引起的脂肪减少不会单一导致身体某一部位或组织的脂肪含量出现非正常状况，而是使人体全身脂肪含量均匀降低，有明显的“塑身”效果。
人体脂肪含量太高容易引发多种疾病，如糖尿病、心脏病等，而体内脂肪含量太低，也同样不利于身体健康。研究人员就认为，这种仅在脂肪细胞中出现的蛋白缺陷是遗传性脂肪代谢障碍的最主要形式，虽具有明显“塑身”功能，但会使身体处于一种非正常瘦身状态，不利于身体健康。
相关研究成果发表在近期的《新英格兰医学杂志》上。（生物谷Bioon.com）
生物谷推荐原文出处：
N Engl J Med 2011; 364:740-748
Perilipin Deficiency and Autosomal Dominant Partial Lipodystrophy
Sheetal Gandotra, Ph.D., Caroline Le Dour, Ph.D., William Bottomley, Ph.D., Pascale Cervera, M.D., Philippe Giral, M.D., Yves Reznik, M.D., Guillaume Charpentier, M.D., Martine Auclair, Marc Delépine, Ph.D., Inês Barroso, Ph.D., Robert K. Semple, Ph.D., Mark Lathrop, Ph.D., Olivier Lascols, Ph.D., Jacqueline Capeau, M.D., Ph.D., Stephen O'Rahilly, M.D., Jocelyne Magré, Ph.D., David B. Savage, M.D., and Corinne Vigouroux, M.D., Ph.D.
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.
Supported by grants from the Wellcome Trust (077016/Z/05/Z, to Drs. Gandotra, Bottomley, Barroso, Semple, O'Rahilly, and Savage), GlaxoSmithKline (to Dr. Savage), the U.K. National Institute for Health Research Cambridge Biomedical Research Centre, the Medical Research Council Center for Obesity and Related Metabolic Disease, Société Francophone du Diabète (Association de Langue Fran?aise pour l'Etude du Diabète et des Maladies Métaboliques) (to Dr. Magré), INSERM (to Drs. Cervera, Lascols, Capeau, Magré, and Vigouroux), and the French Ministère de l'Enseignement Supérieur et de la Recherche (to Dr. Le Dour).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Gandotra and Le Dour contributed equally to this article, as did Drs.Magré, Savage, and Vigouroux.
We thank the patients who participated in these studies, Muriel Meier for help with molecular analyses, Drs. Camille Vatier and Véronique Béréziat and Ms. Sylvie Dumont for help in histologic analyses of adipose tissue, Drs. Soraya Fellahi and Jean-Philippe Bastard for adipokine measurements, Dr. Sylvia Franc for providing clinical and biologic data, Gregory Strachan for training and support for confocal microscopy, Koini Lim for technical support, and Yves Chrétien for help with statistical analyses.
