Exercise-mimicking effect of exogenous lactate administration: Promoting visceral fat reduction via ventromedial hypothalamic SF-1 neurons in female rats.

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.