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

OBJECTIVE: The protective effects of exercise against glucose dysmetabolism have been generally reported. However, the mechanism by which exercise improves glucose homeostasis remains poorly understood. The FGF21-adiponectin axis participates in regulation of glucose metabolism. Elevated levels of FGF21 and decreased levels of adiponectin in obesity indicate the FGF21-adiponectin axis dysfunction. Hence, we investigated whether exercise could improve the FGF21-adiponectin axis impairment and ameliorate disturbed glucose metabolism in diet-induced obese 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 twelve weeks of intervention.

RESULTS: Exercise training led to reduced levels of fasting blood glucose and insulin, improved glucose tolerance and better insulin sensitivity in high-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 that exercise inhibited adipose tissue inflammation, which may contribute to the improvement in the FGF21-adiponectin axis impairment.

CONCLUSIONS: Our data indicate exercise protects against high-fat diet-induced FGF21-adiponectin axis impairment, and may thereby exert beneficial effects on glucose metabolism.