Melanocortin-responsive Kiss1 neurons of the arcuate nucleus drive energy expenditure through glutamatergic signaling to the dorsomedial hypothalamus.

ABSTRACT: Energy expenditure (EE) is essential for metabolic homeostasis, yet its central regulation remains poorly understood. Here, we identify arcuate Kiss1 neurons as key regulators of EE in male mice. Ablation of these neurons induced obesity, while their chemogenetic activation increased brown adipose tissue (BAT) thermogenesis without affecting food intake. This action is mediated by glutamatergic projections from Kiss1^ARC neurons to CART/Lepr-expressing neurons in the dorsomedial hypothalamus, which activate the raphe pallidus-BAT pathway. CRISPR-mediated deletion of the vesicular glutamate transporter 2 (Vglut2) from Kiss1^ARC neurons replicated the obesogenic effect. Furthermore, deletion of the melanocortin 4 receptor (MC4R) from Kiss1 neurons resulted in obesi

SUBMITTER: Talbi R 

PROVIDER: S-EPMC12262500 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature