The melatonergic agonist agomelatine ameliorates high fat diet-induced
obesity in mice through the modulation of the gut microbiome.
Abstract
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.