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Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?

A major challenge of obesity therapy is to sustain clinically relevant weight loss over time. Achieving this goal likely requires both reducing daily caloric intake and increasing caloric expenditure. Over the past decade, advances in pharmaceutical engineering of ligands targeting G protein-coupled...

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Autores principales: Conceição-Furber, Ellen, Coskun, Tamer, Sloop, Kyle W., Samms, Ricardo J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081793/
https://www.ncbi.nlm.nih.gov/pubmed/35547006
http://dx.doi.org/10.3389/fendo.2022.868037
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author Conceição-Furber, Ellen
Coskun, Tamer
Sloop, Kyle W.
Samms, Ricardo J.
author_facet Conceição-Furber, Ellen
Coskun, Tamer
Sloop, Kyle W.
Samms, Ricardo J.
author_sort Conceição-Furber, Ellen
collection PubMed
description A major challenge of obesity therapy is to sustain clinically relevant weight loss over time. Achieving this goal likely requires both reducing daily caloric intake and increasing caloric expenditure. Over the past decade, advances in pharmaceutical engineering of ligands targeting G protein-coupled receptors have led to the development of highly effective anorectic agents. These include mono-agonists of the GLP-1R and dual GIPR/GLP-1R co-agonists that have demonstrated substantial weight loss in experimental models and in humans. By contrast, currently, there are no medicines available that effectively augment metabolic rate to promote weight loss. Here, we present evidence indicating that activation of the GCGR may provide a solution to this unmet therapeutic need. In adult humans, GCGR agonism increases energy expenditure to a magnitude sufficient for inducing a negative energy balance. In preclinical studies, the glucagon-GCGR system affects key metabolically relevant organs (including the liver and white and brown adipose tissue) to boost whole-body thermogenic capacity and protect from obesity. Further, activation of the GCGR has been shown to augment both the magnitude and duration of weight loss that is achieved by either selective GLP-1R or dual GIPR/GLP-1R agonism in rodents. Based on the accumulation of such findings, we propose that the thermogenic activity of GCGR agonism will also complement other anti-obesity agents that lower body weight by suppressing appetite.
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spelling pubmed-90817932022-05-10 Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity? Conceição-Furber, Ellen Coskun, Tamer Sloop, Kyle W. Samms, Ricardo J. Front Endocrinol (Lausanne) Endocrinology A major challenge of obesity therapy is to sustain clinically relevant weight loss over time. Achieving this goal likely requires both reducing daily caloric intake and increasing caloric expenditure. Over the past decade, advances in pharmaceutical engineering of ligands targeting G protein-coupled receptors have led to the development of highly effective anorectic agents. These include mono-agonists of the GLP-1R and dual GIPR/GLP-1R co-agonists that have demonstrated substantial weight loss in experimental models and in humans. By contrast, currently, there are no medicines available that effectively augment metabolic rate to promote weight loss. Here, we present evidence indicating that activation of the GCGR may provide a solution to this unmet therapeutic need. In adult humans, GCGR agonism increases energy expenditure to a magnitude sufficient for inducing a negative energy balance. In preclinical studies, the glucagon-GCGR system affects key metabolically relevant organs (including the liver and white and brown adipose tissue) to boost whole-body thermogenic capacity and protect from obesity. Further, activation of the GCGR has been shown to augment both the magnitude and duration of weight loss that is achieved by either selective GLP-1R or dual GIPR/GLP-1R agonism in rodents. Based on the accumulation of such findings, we propose that the thermogenic activity of GCGR agonism will also complement other anti-obesity agents that lower body weight by suppressing appetite. Frontiers Media S.A. 2022-04-25 /pmc/articles/PMC9081793/ /pubmed/35547006 http://dx.doi.org/10.3389/fendo.2022.868037 Text en Copyright © 2022 Conceição-Furber, Coskun, Sloop and Samms https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Conceição-Furber, Ellen
Coskun, Tamer
Sloop, Kyle W.
Samms, Ricardo J.
Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
title Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
title_full Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
title_fullStr Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
title_full_unstemmed Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
title_short Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
title_sort is glucagon receptor activation the thermogenic solution for treating obesity?
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081793/
https://www.ncbi.nlm.nih.gov/pubmed/35547006
http://dx.doi.org/10.3389/fendo.2022.868037
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