Prior exercise training improves cold tolerance independent of indices associated with non-shivering thermogenesis

KEY POINTS: Mammals defend against cold-induced reductions in body temperature through both shivering and non-shivering thermogenesis. The activation of non-shivering thermogenesis is primarily driven by uncoupling protein-1 in brown adipose tissue and to a lesser degree by the browning of white adipose tissue. Endurance exercise has also been shown to increase markers of white adipose tissue browning. This study aimed to determine whether prior exercise training would alter the response to a cold challenge and if this would be associated with differences in indices of non-shivering thermogenesis. It is shown that exercise training protects against cold-induced weight loss by increasing food intake. Exercise-trained mice were better able to maintain their core temperature, independent of differences in markers of non-shivering thermogenesis. ABSTRACT: Shivering is one of the first defences against cold, and as skeletal muscle fatigues there is an increased reliance on non-shivering thermogenesis. Brown and beige adipose tissues are the primary thermogenic tissues regulating this process. Exercise has also been shown to increase the thermogenic capacity of subcutaneous white adipose tissue. Whether exercise has an effect on the adaptations to cold stress within adipose tissue and skeletal muscle remains to be shown. Male C57BL/6 mice were either subjected to voluntary wheel running or remained sedentary for 12 days. Exercise led to decreased body weight and increased glucose tolerance. Mice were then divided into groups kept at 25°C room temperature or a cold challenge of 4°C for 48 h. Exercised mice were protected against cold-induced reductions in weight and in parallel with increased food intake. Providing exercised mice with the same amount of food as sedentary mice eliminated the protection against cold-induced weight loss. Cold exposure led to greater reductions in rectal temperature in sedentary compared to exercised mice. This protective effect was not explained by differences in the browning of white adipose tissue or brown adipose tissue mass. Similarly, the ability of the β3 -adrenergic agonist CL 316,243 to increase energy expenditure was attenuated in previously exercised mice, suggesting that the activation of uncoupling protein-1 in brown and/or beige adipocytes is not the source of protective effects. We speculate that the protection against cold-induced reductions in rectal temperature could potentially be linked to exercise-induced alterations in skeletal muscle.