Obesogenic effects of warm temperature involve feeding adaptation by preoptic area leptin receptor neurons

The preoptic area (POA) is a well-established regulator of body temperature, but its role in feeding behavior remains underexplored. Our study identifies leptin receptor (Lepr)-expressing neurons in the POA (POA^Lepr) as critical component to suppress food intake (FI) and increase satiety in response to warm ambient temperatures. Utilizing chemogenetic activation in mice of both sexes, we demonstrate that selective activation of POA^Lepr neurons mimics the effects of warm temperatures, leading to a significant reduction in FI. POA^Lepr neurons project to the melanocortin pathway, where activation of melanocortin-4 receptors (MC4R) also suppresses FI in a temperature-dependent manner. Our findings suggest that POA^Lepr neurons integrate thermal and metabolic cues, demonstrating that ambient temperature is an integral part of body weight homeostasis by modulating meal size and satiety via POA^Lepr neurons. These results offer new insights into the neurochemical and functional properties of POA functions, expanding the traditional view that the POA is exclusively involved in thermoregulation and underscoring its broader role in energy balance.