Redox-dependent liver gluconeogenesis impacts different intensity exercise in mice.

ABSTRACT: Hepatic gluconeogenesis produces glucose from various substrates to meet energy demands. However, how these substrates are preferentially used under different conditions remains unclear. Here, we show that preferential supplies of lactate and glycerol modulate hepatic gluconeogenesis, thereby impacting high-intensity and low-intensity exercise capacities, respectively. We find that liver-specific knockout of phosphoenolpyruvate carboxykinase 1 (L-Pck1KO), which blocks gluconeogenesis from lactate, decreases high-intensity exercise capacity but increases low-intensity exercise capacity by enhancing gluconeogenesis from glycerol. Conversely, liver-specific knockout of glycerol kinase (L-GykKO), which inhibits glycerol-derived gluconeogenesis, induces the opposite effects by enhancing glucone

SUBMITTER: Horiuchi T 

PROVIDER: S-EPMC12552127 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature