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MRAP2基因突变与贪吃型肥胖有关
作者:小柯机器人 发布时间:2019/11/11 21:31:51

法国里尔大学Amlie Bonnefond、Philippe Froguel等研究人员合作发现,MRAP2功能缺失突变是伴随高血糖和高血压的贪吃型肥胖的病因。该项研究成果2019年11月7日在线发表在《自然—医学》上。

通过对9418名个体的MRAP2基因进行大规模测序,研究人员确定了23种罕见的杂合变异体,它们与成年人和儿童的肥胖风险增加有关。每个变体的功能评估表明,功能丧失的MRAP2变体对单基因性贪吃肥胖症、高血糖症和高血压具有致病性。这与其他单基因产生的饥饿型肥胖形成了鲜明对比,包括黑色素皮质素4受体缺乏。MRAP2中功能丧失突变所产生的的多种代谢作用可能是由于的各种组织中(包括胰岛在内)MRAP2调节的不同G蛋白偶联受体的失效所致。

据了解,G蛋白偶联受体辅助蛋白MRAP2与啮齿动物的能量控制有关,特别是黑素皮质素-4受体。尽管已在肥胖症患者中报道过了一些MRAP2突变,但它们对肥胖的功能影响仍然难以捉摸。

附:英文原文

Title: Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension

Author: Morgane Baron, Julie Maillet, Marlne Huyvaert, Aurlie Dechaume, Raphal Boutry, Hlne Loiselle, Emmanuelle Durand, Bndicte Toussaint, Emmanuel Vaillant, Julien Philippe, Jrmy Thomas, Amjad Ghulam, Sylvia Franc, Guillaume Charpentier, Jean-Michel Borys, Claire Lvy-Marchal, Math Tauber, Raphal Scharfmann, Jacques Weill, Ccile Aubert, Julie Kerr-Conte, Franois Pattou, Ronan Roussel, Beverley Balkau, Michel Marre, Mathilde Boissel, Mehdi Derhourhi, Stefan Gaget, Mickal Canouil, Philippe Froguel, Amlie Bonnefond

Issue&Volume: 2019-11-07

Abstract: The G-protein-coupled receptor accessory protein MRAP2 is implicated in energy control in rodents, notably via the melanocortin-4 receptor1. Although some MRAP2 mutations have been described in people with obesity13, their functional consequences on adiposity remain elusive. Using large-scale sequencing of MRAP2 in 9,418 people, we identified 23 rare heterozygous variants associated with increased obesity risk in both adults and children. Functional assessment of each variant shows that loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension. This contrasts with other monogenic forms of obesity characterized by excessive hunger, including melanocortin-4 receptor deficiency, that present with low blood pressure and normal glucose tolerance4. The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets. Large-scale sequencing of coding exons of MRAP2 in 9,418 adults and adolescents identifies loss-of-function mutations that are associated with monogenic obesity, hypertension and hyperglycemia.

DOI: 10.1038/s41591-019-0622-0

Source:https://www.nature.com/articles/s41591-019-0622-0

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex