A Combination of Exercise and Yogurt Intake Protects Mice against Obesity by Synergistic Promotion of Adipose...

Exercise exerts many beneficial effects on obesity, but the mechanism remains elusive. Here, we report a previously unidentified role of the lactate receptor GPR81 in exercise. We observed that GPR81 was significantly up-regulated in white adipose tissues (WAT) upon exercise training in both lean and obese mice. Exercise could induce thermogenesis and beige adipocyte development, whereas such an effect was markedly impaired by the deficiency of GPR81. Furthermore, the activation of GPR81 by exercise and lactate supplementation (250 or 500 mg/kg) yielded a synergistic enhancement of WAT browning and thermogenesis. Yogurt is a dairy product enriched with lactate. A combination of exercise and yogurt intake (20 g/kg) synergistically protected mice against high-fat-diet-induced obesity, as evidenced by decreased body weight, ameliorative dyslipidemia, improved glucose tolerance, and reduced hepatic steatosis. Mechanistically, lactate-GPR81 axis might aid in the norepinephrine-stimulated beige adipocyte biogenesis cascade via the Ca²⁺/CaMK pathway. Together, these findings reveal the critical role of lactate-GPR81 signaling in exercise-induced WAT browning and provide a new strategy for personalized diet and lifestyle interventions for obesity management.