Details

Autor(en) / Beteiligte

• Yang, Linda
• Chang, Chih-Chuan
• Sun, Zhe
• Madsen, Dennis
• Zhu, Haisun
• Padkjær, Søren B
• Wu, Xiaoai
• Huang, Tao
• Hultman, Karin
• Paulsen, Sarah J
• Wang, Jishu
• Bugge, Anne
• Frantzen, Jane Boesen
• Nørgaard, Per
• Jeppesen, Jacob Fuglsbjerg
• Yang, Zhiru
• Secher, Anna
• Chen, Haibin
• Li, Xun
• John, Linu Mary
• Shan, Bing
• He, Zhenhua
• Gao, Xiang
• Su, Jing
• Hansen, Kristian T
• Yang, Wei
• Jørgensen, Sebastian Beck

Titel

GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand

Ist Teil von

• Nature medicine, 2017-10, Vol.23 (10), p.1158-1166

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• GDF15 has potent anti-obesity effects, but its receptor was unknown. GFRAL has now been identified as the receptor that mediates GDF15's effects via central actions in the hindbrain. 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.