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GFRAL-expressing neurons suppress food intake via aversive pathways
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GFRAL-expressing neurons suppress food intake via aversive pathways
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GFRAL-expressing neurons suppress food intake via aversive pathways
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Journal Article
GFRAL-expressing neurons suppress food intake via aversive pathways
2021
Overview
The TGFβ 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 α–like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated GfralCre and conditional GfralCreERT 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 GfralCre-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 (CGRPPBN) neurons. Silencing CGRPPBN 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.
Publisher
National Academy of Sciences
Subject
/ Avoidance Learning - drug effects
/ Feeding Behavior - drug effects
/ Female
/ Glial Cell Line-Derived Neurotrophic Factor Receptors - genetics
/ Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism
/ Growth Differentiation Factor 15 - pharmacology
/ Male
/ Mice
/ Parabrachial Nucleus - drug effects
/ Parabrachial Nucleus - physiology
/ Rats
