Effective energy harvesting of Yak by regulating the glucose and lipid metabolism in liver to adapt to the plateau environment

Yaks have successfully adapted to the extreme conditions of the Qinghai-Tibetan Plateau, although the mechanisms underlying their hepatic energy utilization remain poorly understood. Using histological, transcriptomic, and metabolomic approaches, this study compared liver characteristics between yaks and cattle at similar altitudes, as well as between yaks at different altitudes. Results revealed that yaks possess smaller hepatic sinusoids and greater glycogen storage capacity than cattle. Transcriptomic analysis showed that differentially expressed genes (DEGs) in yaks are predominantly involved in carbohydrate and lipid metabolism, with significant up-regulation of key genes such as FBP1 (gluconeogenesis), ACAA1 and ACOX1 (lipolysis), and ACO1 and MDH1 (TCA cycle). High-altitude yaks exhibited even narrower sinusoids and higher glycogen levels, along with DEGs enriched in metabolic pathways including acetyl-CoA synthesis and the TCA cycle. Specifically, G6PC1 was up-regulated, while ACOX1, ACADS, and ACO1 were down-regulated in high-altitude yaks. These findings suggest that yaks maintain energy homeostasis through enhanced lipolytic metabolism and increased TCA cycle activity. Compared to low-altitude yaks, those at high elevations appear to rely more on oxidative phosphorylation for energy production, highlighting key metabolic adaptations that support survival in hypoxic environments.