Suppression of obesity by melatonin through increasing energy expenditure and accelerating lipolysis in mice fed a high-fat diet

Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.

Male C57BL/6 J mice received a high-fat diet (HFD) or normal chow, accompanied by intraperitoneal injection of 20 mg/kg melatonin for 12 weeks. FGF21-/- mice consumed an HFD with or without melatonin for 8 weeks.

Melatonin attenuated weight gain, insulin resistance, adipocyte hypertrophy, inflammation, and hepatic steatosis induced by the HFD and increased energy expenditure. Furthermore, melatonin improved cold tolerance by increasing BAT uncoupling protein 1 (UCP1) expression and producing heat. Notably, melatonin resulted in a shift in energy metabolism favouring the utilization of fat, and it increased FGF21 in circulating and metabolic tissues and skeletal muscle phosphorylation of AMP-activated protein kinase. However, melatonin did not protect against obesity, insulin resistance, and energy expenditure in HFD-fed FGF21-/- mice. Conclusions: Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.