First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Curr Obes Rep. 2020 Sep;9(3):255-271. doi: 10.1007/s13679-020-00396-9.
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.
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.
目的综述：本文综述了肠激素在能量稳态调节中的作用及其相互作用，描述了肥胖及体重减轻时肠激素的适应性变化，并总结了基于肠激素的肥胖治疗方法的现有证据。
最新发现：肠激素在调节摄食行为、能量和葡萄糖稳态方面发挥着关键作用。肠激素反应失调被认为与肥胖的发生和持续存在有关。总结肥胖时主要的肠激素变化，肥胖个体表现为餐后ghrelin 抑制减弱、餐前 ghrelin 峰值丧失、昼夜 ghrelin 变化受损以及空腹和餐后厌食肽水平降低。肠激素水平的适应性改变与体重反弹有关，从而使低热量饮食干预复杂化，也可以进一步解释减重手术后的显著体重减轻和代谢改善。目前正在研究大量模拟减重手术后肠激素变化的化合物，为肥胖的药物治疗带来了一个新时代。目前的趋势是结合不同的肠激素受体激动剂，同时针对多个系统，以尽可能地复制减重手术后的肠激素环境，并规避与饮食能量限制相关的代偿性适应性变化。越来越多的临床前和早期临床试验显示，双重或三重肠肽受体激动剂在减轻体重和改善血糖方面具有附加益处。肠激素是能量和葡萄糖稳态的有效调节剂。靶向其水平或受体的治疗策略有望成为治疗肥胖和高血糖患者的一种有前途的方法。
