Cell Reports
Volume 31, Issue 3, 21 April 2020, 107543
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GDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss

https://doi.org/10.1016/j.celrep.2020.107543Get rights and content
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Highlights

  • Acute GDF15 systemic delivery induces visceral malaise, anorexia, and body weight loss

  • Chronic GDF15 exposure triggers visceral malaise that does not decline over time

  • GDF15 conditions food-aversive responses persisting beyond its acute anorectic action

  • GDF15’s visceral malaise and anorectic effects do not require slowed gastric emptying

Summary

The anorectic and weight-suppressive effects of growth differentiation factor-15 (GDF15) are attracting considerable attention for treating obesity. Current experiments in rats investigate whether GDF15 induces an aversive visceral malaise-based state that mediates its acute anorectic effect and, through aversion conditioning, exerts longer-term anorexia. Visceral malaise, conditioned affective food responses (taste reactivity), gastric emptying (GE), food intake, and body weight are evaluated after acute and chronic systemic dosing of GDF15 or long-acting Fc-GDF15. Pica, a marker of visceral malaise, is present at all anorectic GDF15 doses. Moreover, malaise induced by GDF15 does not decline over time, suggesting the lack of an improved tolerance after prolonged exposure. One association between GDF15 and novel food conditions a disgust/aversive response that persists beyond GDF15 acute action. Delayed GE is not a requirement for GDF15-induced anorexia. Clinical studies are required to evaluate whether GDF15’s aversive-state-based anorexia will be contraindicated as an obesity treatment.

Keywords

MIC-1
pica
taste reactivity
food aversion conditioning
affective response to food
gastric emptying
GFRAL
PBN
hindbrain

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