Liu Peng, Ji Yaoting, Yuen Tony, Rendina-Ruedy Elizabeth, DeMambro Victoria E, Dhawan Samarth, Abu-Amer Wahid, Izadmehr Sudeh, Zhou Bin, Shin Andrew C, Latif Rauf, Thangeswaran Priyanthan, Gupta Animesh, Li Jianhua, Shnayder Valeria, Robinson Samuel T, Yu Yue Eric, Zhang Xingjian, Yang Feiran, Lu Ping, Zhou Yu, Zhu Ling-Ling, Oberlin Douglas J, Davies Terry F, Reagan Michaela R, Brown Aaron, Kumar T Rajendra, Epstein Solomon, Iqbal Jameel, Avadhani Narayan G, New Maria I, Molina Henrik, van Klinken Jan B, Guo Edward X, Buettner Christoph, Haider Shozeb, Bian Zhuan, Sun Li, Rosen Clifford J, Zaidi Mone
Department of Medicine, and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
School and Hospital of Stomatology, Wuhan University, and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan, Hubei 430079, China.
Nature. 2017 Jun 1;546(7656):107-112. doi: 10.1038/nature22342. Epub 2017 May 24.
Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the β-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the β-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.
更年期与骨质流失和内脏脂肪增多有关。一种靶向垂体激素促卵泡激素(Fsh)β亚基的多克隆抗体可增加小鼠的骨量。在此,我们报告该抗体可显著减少野生型小鼠的脂肪组织,模拟Fsh受体基因Fshr的遗传单倍体不足。该抗体还会引起显著的米色化,增加细胞线粒体密度,激活棕色脂肪组织并增强产热。这些作用源于抗体与Fsh的β亚基特异性结合以阻断其作用。我们的研究揭示了同时治疗肥胖症和骨质疏松症的机会。