| Literature DB >> 28846099 |
Linda Yang1, Chih-Chuan Chang1, Zhe Sun1, Dennis Madsen2, Haisun Zhu1, Søren B Padkjær2, Xiaoai Wu1, Tao Huang1, Karin Hultman2, Sarah J Paulsen2, Jishu Wang1, Anne Bugge2, Jane Boesen Frantzen2, Per Nørgaard2, Jacob Fuglsbjerg Jeppesen2, Zhiru Yang1, Anna Secher2, Haibin Chen1, Xun Li1, Linu Mary John2, Bing Shan1, Zhenhua He1, Xiang Gao1, Jing Su1, Kristian T Hansen2, Wei Yang1, Sebastian Beck Jørgensen2.
Abstract
Growth differentiation factor 15 (GDF15; also known as MIC-1) is a divergent member of the TGF-β superfamily and is associated with body-weight regulation in humans and rodents. However, the cognate receptor of GDF15 is unknown. Here we show that GDF15 binds specifically to GDNF family receptor α-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF15 stimulation. We also found that GDF15-mediated reductions in food intake and body weight of mice with obesity were abolished in GFRAL-knockout mice. We further found that GFRAL expression was limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism. Lastly, given that GDF15 did not increase energy expenditure in treated mice with obesity, the anti-obesity actions of the cytokine are likely driven primarily by a reduction in food intake.Entities:
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Year: 2017 PMID： 28846099 DOI： 10.1038/nm.4394
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440