Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain.
Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain.
Biomed Pharmacother. 2022 Sep;153:113445. doi: 10.1016/j.biopha.2022.113445. Epub 2022 Jul 22.
Melatonin has shown beneficial effects on obesity, both in humans and experimental models, via regulating the altered circadian rhythm and thus ameliorating the gut dysbiosis associated with this metabolic condition. However, its clinical use is limited, mostly due to its short half-life. Agomelatine is an agonist of the melatonin receptors that could be used to manage obesity and offer a better profile than melatonin.
Male C57BL/6 mice were fed a high fat diet and orally treated for five weeks with agomelatine, or melatonin or metformin, used as control drugs. Metabolic profile, inflammatory status, vascular dysfunction and intestinal microbiota composition were assessed.
Agomelatine lessened body weight gain, enhanced glucose and lipid metabolisms, and improved insulin resistance. It also reduced the obesity-associated inflammatory status and endothelial dysfunction, probably linked to its effect on gut dysbiosis, consisting of the restoration of bacterial populations with key functions, such as short chain fatty acid production.
Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities.
褪黑素通过调节紊乱的昼夜节律，从而改善与这种代谢状况相关的肠道菌群失调，已显示出对肥胖具有有益作用，无论是在人类还是实验模型中。然而，其临床应用受到限制，主要是由于其半衰期短。阿戈美拉汀是褪黑素受体的激动剂，可用于治疗肥胖症，并提供比褪黑素更好的效果。
雄性 C57BL/6 小鼠喂食高脂肪饮食，并口服给予阿戈美拉汀、褪黑素或二甲双胍治疗五周，后两者用作对照药物。评估代谢特征、炎症状态、血管功能障碍和肠道微生物群落组成。
阿戈美拉汀减轻了体重增加，改善了葡萄糖和脂质代谢，并改善了胰岛素抵抗。它还降低了与肥胖相关的炎症状态和内皮功能障碍，这可能与其对肠道菌群失调的影响有关，包括恢复具有关键功能的细菌种群，例如短链脂肪酸的产生。
阿戈美拉汀可被视为治疗人类肥胖及其相关合并症的新型治疗工具。
