Integration of sensory information via central thermoregulatory leptin targets

Abstract

The adipocyte derived hormone leptin acts in the brain to regulate body weight, food intake and energy expenditure. Even though it is well accepted that leptin regulates energy expenditure at least in part by modulating thermogenesis, the exact mechanisms are not clear. Particularly, it is unclear which central circuits regulate thermogenic leptin actions and if and how these may interact with feeding circuits. Within the last decade our understanding of central thermoregulatory circuits has increased substantially and allowed the identification of leptin target neurons (those expressing the long form leptin receptor — LepRb) that are involved in the sympathetic control of the heat generating brown adipose tissue (BAT). Indeed, LepRb neurons in the preoptic area and dorsomedial hypothalamus are part of the known thermoregulatory circuits controlling sympathetic premotor neurons that are located in the raphe pallidus. Thermoregulatory control and food intake are both regulated by leptin signaling pathways, even though distinct neuronal pathways have been described, respectively. Nevertheless, feeding status and control of body temperature and energy expenditure are tightly interconnected, but it is unknown how these aspects are connected within leptin signaling pathways to result in appropriate output signals (e.g. BAT thermogenesis). Indeed, cold-induced thermogenesis is potently blocked during fasting, which instead triggers an active decrease in energy expenditure and body temperature, a state known as torpor. In this article we will review recent data characterizing central thermoregulatory LepRb pathways and speculate on potential integration mechanisms that may relay anorexic and thermoregulatory leptin action to control energy homeostasis.