Mammals can maintain stable body temperature due to various thermogenic mechanisms, which are either (i) facultative (occurring only under specific conditions), such as muscle shivering; or (ii) adaptive (adjusting their capacity according to long-term needs), including non-shivering thermogenesis (NST) in brown adipose tissue (BAT), which depends on uncoupling protein 1 (UCP1). Several alternative thermogenic mechanisms have been suggested. However, they are still poorly defined. We have characterized organ-specific contributions to NST in mice with different genetic backgrounds, obesity-prone C57BL/6J mice, and obesity-resistant A/J mice (1). Mice of both strains could acclimate to cold, initially using muscle shivering. Prolonged cold exposure led to the activation of NST in BAT in C57BL/6J mice. Surprisingly, A/J mice failed to activate BAT but increased NST in skeletal muscle, mediated by sarcolipin-induced uncoupling of sarcoplasmic reticulum calcium ATPase pump activity. Thus, NST in skeletal muscle could be adaptively augmented in the face of insufficient NST in BAT. It may protect from cold and provide resistance to obesity more effectively than BAT (1). Recently, we aimed to learn whether muscle NST could be permanently affected by cold exposure of mouse pups. C57BL/6J and A/J mice born and maintained at thermoneutrality (30 °C) or mild cold (20 °C) until six weeks of age were moved to 30 °C until 3 months of age. Proteomic analysis performed on the gastrocnemius muscle of 3-month-old mice revealed a lasting effect of the ambient temperature on lipid metabolism in A/J but not in B6 mice. Thus, the capacity for muscle NST of obesity-resistant mice could be imprinted by ambient temperature during early weeks after birth. Regarding adult humans, the oxidative capacity of skeletal muscle is several-fold greater than in BAT. Thus, only a relatively small increase in muscle NST could significantly reduce body fat.
This project is supported by the Czech Science Foundation (22-07004S).