| First Author | Sabatini PV | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 8 | PubMed ID | 33593916 |
| Mgi Jnum | J:316128 | Mgi Id | MGI:6508736 |
| Doi | 10.1073/pnas.2021357118 | Citation | Sabatini PV, et al. (2021) GFRAL-expressing neurons suppress food intake via aversive pathways. Proc Natl Acad Sci U S A 118(8):e2021357118 |
| abstractText | The TGFbeta cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor alpha-like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated Gfral (Cre) and conditional Gfral (CreERT) mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating Gfral (Cre) -expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRP(PBN)) neurons. Silencing CGRP(PBN) neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated pathophysiologic signals to suppress nutrient uptake and absorption. |
