| First Author | Yang L | Year | 2017 |
| Journal | Nat Med | Volume | 23 |
| Issue | 10 | Pages | 1158-1166 |
| PubMed ID | 28846099 | Mgi Jnum | J:251981 |
| Mgi Id | MGI:6103585 | Doi | 10.1038/nm.4394 |
| Citation | Yang L, et al. (2017) GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat Med 23(10):1158-1166 |
| abstractText | Growth differentiation factor 15 (GDF15; also known as MIC-1) is a divergent member of the TGF-beta 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 alpha-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. |
