Identification of a neural basis for energy expenditure in the mouse arcuate hypothalamus

Abstract

Given the evolutionary instinct for caloric intake and frequent weight rebound after diet or drug cessation, increasing energy expenditure emerges as an alternative obesity treatment. Environmental cues such as cold and seasonal light prompt the brain to adjust energy expenditure, yet the coordinating neural mechanisms remain poorly understood. Here, we identify a hypothalamic GABAergic neuronal subtype, marked by Crabp1, that targets multiple nuclei to regulate energy expenditure in mice. Silencing Crabp1 neurons reduces physical activity, body temperature, and adaptive thermogenesis, leading to obesity, whereas activation increases energy expenditure and mitigates diet-induced obesity. Structural and functional analyses reveal that Crabp1 neurons promote energy metabolism through a "one-to-many" projection pattern. While Crabp1 neurons are activated by cold exposure and physical activity, prolonged light exposure abrogates their firing, which mediates light-induced metabolic disorder. Together, we reveal a neural basis that integrates various physiological and environmental stimuli to control energy expenditure and body weight.

Keywords: Crabp1 neurons; arcuate nucleus; cold exposure; energy expenditure; exercise; feeding behavior; hypothalamus; light pollution; metabolic disorder; obesity.