GDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss.

Abstract:

: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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Borner T,Wald HS,Ghidewon MY,Zhang B,Wu Z,De Jonghe BC,Breen D,Grill HJ

doi

10.1016/j.celrep.2020.107543

subject

Has Abstract

pub_date

2020-04-21 00:00:00

pages

107543

issue

3

issn

2211-1247

pii

S2211-1247(20)30443-5

journal_volume

31

pub_type

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