GFRAL-expressing neurons suppress food intake via aversive pathways
Paul V. Sabatini, Henriette Frikke‐Schmidt, Joe Arthurs, Desiree Gordian, Anita Patel, Alan C. Rupp, Jessica M. Adams, Jine Wang, Sebastian B. Jørgensen, David P. Olson, Richard D. Palmiter, Martin G. Myers, Randy J. Seeley
Abstract
Significance Growth and differentiation factor-15 (GDF-15) acts through its receptor, GFRAL, expressed within the area postrema to reduce food intake and body weight. However, we do not yet understand GFRAL neuron transcriptional profile, regulation, the direct downstream target sites of GFRAL neurons, or the necessary cell types required for GDF-15 activity. Herein, we identify the genetic signature of GFRAL neurons and show that these cells are positively regulated by a number of aversive stimuli, project to both the nucleus of the solitary tract and more densely to the parabrachial nucleus, and that CGRP PBN neurons are required for the aversive and anorectic effects of GDF-15.