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

Abstract

Given the evolutionary instinct for caloric intake and the tendency for weight rebound after discontinuing dietary interventions or medications, increasing energy expenditure emerges as an alternative obesity treatment. However, neural regulation of energy expenditure remains poorly understood. Here, we report that a hypothalamic neuronal subtype, characterized by Crabp1 expression, establishes connections with multiple hypothalamic nuclei to regulate energy expenditure in mice. Inactivation of Crabp1 neurons reduces physical activity, body temperature, and adaptive thermogenesis, leading to an obese phenotype. Conversely, activation of these neurons 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 rapidly activated by cold exposure and physical activity, prolonged light exposure abrogates their firing and may mediate light-induced metabolic disorder. Together, we reveal a neural basis that integrate various physiological and environmental stimuli to control energy expenditure and body weight.