Chrysi Koliaki1, Stavros Liatis2, Maria Dalamaga3, Alexander Kokkinos2. 1. First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece. ckoliaki@yahoo.com. 2. First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece. 3. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Abstract
PURPOSE OF REVIEW: This review provides an update on the role of gut hormones and their interactions in the regulation of energy homeostasis, describes gut hormone adaptations in obesity and in response to weight loss, and summarizes the current evidence on the role of gut hormone-based therapies for obesity treatment. RECENT FINDINGS: Gut hormones play a key role in regulating eating behaviour, energy and glucose homeostasis. Dysregulated gut hormone responses have been proposed to be pathogenetically involved in the development and perpetuation of obesity. Summarizing the major gut hormone changes in obesity, obese individuals are characterized by blunted postprandial ghrelin suppression, loss of premeal ghrelin peaks, impaired diurnal ghrelin variability and reduced fasting and postprandial levels of anorexigenic peptides. Adaptive alterations of gut hormone levels are implicated in weight regain, thus complicating hypocaloric dietary interventions, and can further explain the profound weight loss and metabolic improvement following bariatric surgery. A plethora of compounds mimicking gut hormone changes after bariatric surgery are currently under investigation, introducing a new era in the pharmacotherapy of obesity. The current trend is to combine different gut hormone receptor agonists and target multiple systems simultaneously, in order to replicate as closely as possible the gut hormone milieu after bariatric surgery and circumvent the counter-regulatory adaptive changes associated with dietary energy restriction. An increasing number of preclinical and early-phase clinical trials reveal the additive benefits obtained with dual or triple gut peptide receptor agonists in reducing body weight and improving glycaemia. Gut hormones act as potent regulators of energy and glucose homeostasis. Therapeutic strategies targeting their levels or receptors emerge as a promising approach to treat patients with obesity and hyperglycaemia.
PURPOSE OF REVIEW: This review provides an update on the role of gut hormones and their interactions in the regulation of energy homeostasis, describes gut hormone adaptations in obesity and in response to weight loss, and summarizes the current evidence on the role of gut hormone-based therapies for obesity treatment. RECENT FINDINGS: Gut hormones play a key role in regulating eating behaviour, energy and glucose homeostasis. Dysregulated gut hormone responses have been proposed to be pathogenetically involved in the development and perpetuation of obesity. Summarizing the major gut hormone changes in obesity, obese individuals are characterized by blunted postprandial ghrelin suppression, loss of premeal ghrelin peaks, impaired diurnal ghrelin variability and reduced fasting and postprandial levels of anorexigenic peptides. Adaptive alterations of gut hormone levels are implicated in weight regain, thus complicating hypocaloric dietary interventions, and can further explain the profound weight loss and metabolic improvement following bariatric surgery. A plethora of compounds mimicking gut hormone changes after bariatric surgery are currently under investigation, introducing a new era in the pharmacotherapy of obesity. The current trend is to combine different gut hormone receptor agonists and target multiple systems simultaneously, in order to replicate as closely as possible the gut hormone milieu after bariatric surgery and circumvent the counter-regulatory adaptive changes associated with dietary energy restriction. An increasing number of preclinical and early-phase clinical trials reveal the additive benefits obtained with dual or triple gut peptide receptor agonists in reducing body weight and improving glycaemia. Gut hormones act as potent regulators of energy and glucose homeostasis. Therapeutic strategies targeting their levels or receptors emerge as a promising approach to treat patients with obesity and hyperglycaemia.
Entities:
Keywords:
Appetite; Energy homeostasis; Gut hormones; Medical bypass; Obesity; Satiety
Authors: Robert H Lustig; David Collier; Christopher Kassotis; Troy A Roepke; Min Ji Kim; Etienne Blanc; Robert Barouki; Amita Bansal; Matthew C Cave; Saurabh Chatterjee; Mahua Choudhury; Michael Gilbertson; Dominique Lagadic-Gossmann; Sarah Howard; Lars Lind; Craig R Tomlinson; Jan Vondracek; Jerrold J Heindel Journal: Biochem Pharmacol Date: 2022-04-05 Impact factor: 6.100
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