Regulation of thermogenic adipocytes during fasting and cold

Cold exposure activates brown and brown-like adipocytes that dissipate large amounts of glucose and fatty acids via uncoupling protein 1 (UCP1) to drive non-shivering thermogenesis (NST). Evidence for the existence of these thermogenic adipocytes in adult humans gave rise to a renaissance in research on brown adipose tissue, establishing it as linchpin of energy homeostasis and metabolic health. Besides low ambient temperature, shortage or excess of food affect thermoregulation. Upon high caloric meals thermogenic adipocytes burn excess calories and maintain energy balance. In contrast, in conditions of nutrient deprivation, counter-regulatory mechanisms prevent thermogenic adipocytes from "wasting" energy substrates that need to be conserved. In this review, we discuss cell-autonomous mechanisms, metabolites, and hormones that modify NST in response to nutrient fluctuations. In particular, we focus on how thermogenic adipocytes balance thermogenesis with systemic energy homeostasis during fasting periods.