Exercise-mimicking effect of exogenous lactate administration: Promoting visceral fat reduction via ventromedial hypothalamic SF-1 neurons in female rats.
Du J, Zhang Z, Han J, Tian S, Chang M, Chen W et al. · American journal of physiology. Endocrinology and metabolism · 2026
Lactate, a metabolic product of high-intensity training, may possess exercise-mimicking effects that promote fat loss via the hypothalamic-adipose axis, yet its neuronal targets remain unclear. This study investigated whether lactate administration mimics HIT-induced fat loss through steroidogenic factor-1 (SF-1) neurons in the ventromedial hypothalamus (VMH). Female SD rats fed a high-fat diet were subjected to a 6-week intervention. The
Results: showed that chronic lactate administration independently reduced Visceral adipose tissue (VAT) mass and enhanced the resting fat oxidation rate more effectively than moderate-intensity aerobic training (AT), which conversely suppressed post-exercise lipolysis. The VAT loss was accompanied by neuroplastic changes in the VMH and upregulated markers of sympathetic capacity in adipose tissue. In contrast, chemogenetic inhibition of VMH SF-1 neurons using DREADDs reversed the lactate-mediated electrophysiological changes and abolished the elevation in resting metabolic rate (RMR), confirming the necessity of this neuronal population for the metabolic effects of lactate. These
Findings: demonstrate that lactate acts as a central exerkine, activating VMH SF-1 neurons, which correlates with an upregulated capacity for SNS-mediated VAT reduction, thereby providing a mechanistic explanation for the superior efficacy of HIT in managing central obesity.