英國劍橋大學(xué)研究人員最新發(fā)現(xiàn)一種罕見的遺傳疾病,，患者的圍脂滴蛋白基因變異會(huì)導(dǎo)致其脂肪細(xì)胞功能受到影響，從而使其身體脂肪含量均勻降低,，“瘦身”效果明顯,。
人體許多細(xì)胞中都會(huì)存儲(chǔ)少量脂肪，而絕大多數(shù)脂肪則存儲(chǔ)于白色脂肪細(xì)胞中：該細(xì)胞90%的空間都被脂質(zhì)滴所占據(jù),。劍橋大學(xué)的最新一項(xiàng)研究發(fā)現(xiàn),，脂肪細(xì)胞中一種圍脂滴蛋白基因（PLIN1基因）的兩個(gè)結(jié)構(gòu)移位突變，會(huì)導(dǎo)致脂肪細(xì)胞脂質(zhì)存儲(chǔ)功能錯(cuò)亂,，使患者體內(nèi)脂肪含量降低,。實(shí)驗(yàn)發(fā)現(xiàn)，有此基因變異的實(shí)驗(yàn)鼠有時(shí)甚至無法生產(chǎn)圍脂滴蛋白,。與通常的脂肪代謝障礙不同,，該基因變異引起的脂肪減少不會(huì)單一導(dǎo)致身體某一部位或組織的脂肪含量出現(xiàn)非正常狀況，而是使人體全身脂肪含量均勻降低,，有明顯的“塑身”效果,。
人體脂肪含量太高容易引發(fā)多種疾病，如糖尿病,、心臟病等,，而體內(nèi)脂肪含量太低，也同樣不利于身體健康,。研究人員就認(rèn)為,，這種僅在脂肪細(xì)胞中出現(xiàn)的蛋白缺陷是遺傳性脂肪代謝障礙的最主要形式，雖具有明顯“塑身”功能,，但會(huì)使身體處于一種非正常瘦身狀態(tài),，不利于身體健康。
相關(guān)研究成果發(fā)表在近期的《新英格蘭醫(yī)學(xué)雜志》上,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
