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

Sep 30, 2026

Uploaded by Kyle

Yaks have adapted to extreme conditions on the Qinghai-Tibetan Plateau, yet hepatic energy utilization mechanisms remained unclear. Using histology, transcriptomics, and metabolomics, the study compared yak and cattle liver at similar altitudes and compared yaks across altitudes. Yak livers showed smaller sinusoids and higher glycogen storage than cattle, with differential genes enriched in carbohydrate and lipid metabolism. High-altitude yaks displayed narrower sinusoids, elevated glycogen, increased TCA-cycle-related activity, and altered regulation of key glucose and lipid genes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Introduction

Adaptive challenges on the Qinghai-Tibetan Plateau

Yak metabolic adaptation: genes and physiology

Liver as an energy metabolism hub

Evidence from other species

Yak liver-centered adaptive strategy

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Effective energy harvesting of Yak by regulating the glucose and lipid metabolism in liver to adapt to the plateau environment Jingqing Ma1, Na Song1, Nating Huang1, Zhanlei Rong2, Jingyi Li1, Shuwen Wang1, Xun Zhang1, Qing Wei1 & Jiarui Chen1􀀍 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 andACOX1 (lipolysis), andACO1 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 theTCA cycle. Specifically, G6PC1 was upregulated, while ACOX1, ACADS, andACO1 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. Keywords Yak, Liver, Energy metabolism, Qinghai-Tibetan plateau The Qinghai-Tibetan Plateau, one of the highest and harshest geographical regions globally, features extreme ecological conditions such as hypoxia, low temperatures, intense UV radiation, and nutrient scarcity1. Longterm natural selection has driven indigenous species to evolve a series of adaptive phenotypes and molecular mechanisms to sustain their survival and reproduction in high-altitude environments2. For example, plateau pika (Ochotona curzoniae) significantly reduces hypoxia-induced myocardial injury by upregulating the key gene EPAS1 in the hypoxia-inducible factor pathway, thereby enhancing its hypoxic tolerance3. In highaltitude mammals like Myospalacinae, positive selection acts on genes involved in energy transport and enzyme catalytic functions, significantly optimizing their energy metabolism efficiency to cope with the high-energydemanding survival environment4. Furthermore, in human populations residing at high altitudes, HIF-2α has been found to exhibit strong signals of positive selection within the HIF signaling pathway, highlighting its critical role in hypoxia adaptation5.Yaks (Bos grunniens) have developed multifaceted adaptive changes over time to survive in the Qinghai-Tibetan Plateau environment. Studies have shown that several key genes related to hypoxic response, such as HIF1A, VEGFA, and EPAS1, are significantly upregulated in the tissues of plateau yaks, which helps regulate angiogenesis, oxygen transport, and cellular metabolic reprogramming, thus maintaining their physiological homeostasis under hypoxic conditions6,7. Moreover, yak colostrum is rich in active glycometabolites such as UDP-galactose, N-acetylglucosamine, and UDP-glucose, which not only provide energy support for newborns but also participate in hypoxia adaptation and immune regulation through glycosylation modifications8. Recent studies have also found that under high-altitude hypoxic conditions, the expression of mitochondrial dynamics-related gene FIS1 is significantly upregulated in yak kidneys, suggesting that it promotes mitochondrial fission to maintain mitochondrial network dynamic balance and functional integrity, thereby enhancing cellular tolerance

FAQs

What was the main goal of the yak energy metabolism study?

To clarify how yak livers utilize energy and what mechanisms regulate hepatic glucose and lipid metabolism when adapting to plateau environments.

How did yak liver characteristics differ from cattle at similar altitudes?

Yaks had smaller hepatic sinusoids and greater glycogen storage capacity than cattle, accompanied by gene expression patterns linked to carbohydrate and lipid metabolism.

What metabolic changes were more pronounced in high-altitude yaks?

High-altitude yaks showed even narrower sinusoids and higher glycogen levels, with differentially expressed genes enriched in pathways such as acetyl-CoA synthesis and the TCA cycle, indicating stronger oxidative phosphorylation reliance.

Sep 30, 2026

Uploaded by Kyle