Exendin-4 improves thermogenic capacity by regulating fat metabolism on brown adipose tissue in mice with diet-induced obesity.

OBJECTIVE: This study aimed to investigate the benefits of exendin-4 treatment on brown adipose tissue (BAT) in C57BL/6J mice with high-fat diet (HFD)-induced obesity. METHODS: We examined the effects of exendin-4 on body adiposity and the level of genes associated with adipogenesis, glucose/lipid uptake, lipolysis, and thermogenesis in mice with diet-induced obesity. RESULTS: Exendin-4 treatment deceased body weight, serum-free fatty acid, and triglyceride levels in HFD-induced obese C57BL/6J mice. Exendin-4 treatment increased the expression of genes associated with adipogenesis, glucose/lipid uptake, lipolysis, and thermogenesis in BAT. Compared with HFD-fed mice, exendin-4 treatment also exhibited elevated energy expenditure and reduced respiratory quotient, but showed similar food intake and locomotor activity. CONCLUSIONS: Exendin-4 treatment reduced high-fat-induced obesity by decreasing adiposity and increasing thermogenesis. This result suggests that GLP-1 agonist may be a new approach to combat obesity by shifting the energy balance from obesogenesis to thermogenesis.