Exercise ameliorates the FGF21-adiponectin axis impairment in diet-induced obese mice

Abstract

Objective: The protective effects of exercise against glucose dysmetabolis m have been generally reported. However, the mechanism by which exercise im proves glucose homeostasis remains poorly understood. The FGF21-adiponectin axis participates in the regulation of glucose metabolism. Elevated levels of FGF21 and decreased levels of adiponectin in obesity indicate FGF21-adiponectin axis dysfu nction. Hence, we investigated whether exercise could improve the FGF21-adiponectin axis impairment and ameliorate disturbed glucose metabolism in diet-induced obe se mice. Methods: Eight-week-old C57BL/6J mice were randomly assigned to three groups: Low-fat diet control group, high-fat diet group and high-fat diet plus exercise group. Glucose metabolic parameters, the ability of FGF21 to induce adiponectin, FGF21 receptors and co-receptor levels and adipose tissue inflammation were evaluated after 12 weeks of intervention. Results: Exercise training led to reduced levels of fasting blood gluco se and insulin, improved glucose tolerance and better insulin sensitivity in hi gh-fat diet-induced obese mice. Although serum FGF21 levels were not significantly changed, both total and high-molecular-weight adiponectin concentrations were markedly enhanced by exercise. Importantly, exercise protected against high-fat diet-induced impaired ability of FGF21 to stimulate adiponectin secretion. FGF21 co-receptor, β-klotho, as well as receptors, FGFR1 and FGFR2, were upregulated by exercise. We also found th at exercise inhibited adipose tissue inflammation, which may contribute to the improve ment in the FGF21-adiponectin axis impairment. Conclusions: Our data indicate exercise protects against high-fat diet-indu ced FGF21-adiponectin axis impairment, and may thereby exert benefic ial effects on glucose metabolism.