The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome Díez Echave, Patricia Vezza, Teresa Algieri, Francesca Ruiz Malagón, Antonio Jesús Hidalgo García, Laura García García, Federico Morón Romero, María Rocío Sánchez Santos, Manuel Toral, Marta Romero Pérez, Miguel Duarte Pérez, Juan Manuel Garrido Mesa, José Rodríguez Cabezas, María Elena Rodríguez Nogales, Alba Gálvez Peralta, Julio Juan Agomelatine Melatonin Metabolism Metformin Microbiome Obesity Background and purpose: 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. Experimental approach: 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. Key results: 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. Conclusions and implications: Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities. 2022-09-15T08:28:50Z 2022-09-15T08:28:50Z 2022-07-22 journal article Patricia Diez-Echave... [et al.]. The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome, Biomedicine & Pharmacotherapy, Volume 153, 2022, 113445, ISSN 0753-3322, [https://doi.org/10.1016/j.biopha.2022.113445] http://hdl.handle.net/10481/76707 10.1016/j.biopha.2022.113445 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier