bioRxiv. September 21, 2025
The Hypothalamic–Pituitary–Adrenal Axis Orchestrates 1 Energy Homeostasis during Cold Exposure
Abstract
Cold exposure stimulates the sympathetic nervous system (SNS) to activate brown fat thermogenesis and maintain optimal body temperature, while simultaneously triggering compensatory hyperphagia to restore energy balance. The mechanisms coordinating energy expenditure and intake, however, remain unclear.Here, we reveal that the hypothalamic-pituitary-adrenal (HPA) axis plays a dual role in this process: endogenous adrenocorticotropic hormone (ACTH) directly stimulates the melanocortin-2 receptor (MC2R) in brown adipocytes to promote thermogenesis, whereas glucocorticoids drive cold-induced hyperphagia and act permissively to enhance ACTH-mediated energy expenditure. These findings uncover previously and act permissively to enhance ACTH-mediated energy expenditure. These findings uncover previously and act permissively to enhance ACTH-mediated energy expenditure. These findings uncover previously responses associated with increased energy expenditure, with potential implications for obesity treatment.
Products: DHK28601, Research Grade Anti-Human ACTH (ALD1613)
