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

Autor:	Borner T; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA., Wald HS; Institute of Diabetes, Obesity and Metabolism and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA., Ghidewon MY; Institute of Diabetes, Obesity and Metabolism and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA., Zhang B; Internal Medicine Research Unit, Pfizer Global R&D, 1 Portland Street, Cambridge, MA, USA., Wu Z; Internal Medicine Research Unit, Pfizer Global R&D, 1 Portland Street, Cambridge, MA, USA., De Jonghe BC; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Diabetes, Obesity and Metabolism and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA., Breen D; Internal Medicine Research Unit, Pfizer Global R&D, 1 Portland Street, Cambridge, MA, USA., Grill HJ; Institute of Diabetes, Obesity and Metabolism and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: grill@sas.upenn.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Apr 21; Vol. 31 (3), pp. 107543.
DOI:	10.1016/j.celrep.2020.107543
Abstrakt:	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. Competing Interests: Declaration of Interests Research funding from Pfizer to H.J.G. was used to support these studies. B.C.D.J. also receives research funds from Pfizer. H.J.G. is a consultant and advisory board member for Novo Nordisk. B.C.D.J. also received funding from Eli Lilly that was not used in support of these studies. T.B. and B.C.D.J. are co-inventors and owners of a patent for a proprietary compound related to the GDF15/GFRAL system (serial no. 62/801,391). B.Z., Z.W., and D.B. are employees of Pfizer. All other authors declare no competing interests. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu