Comparative transcriptomic analysis of AMPK function in lung tissues of yaks and cattle at the same altitude

AMP-activated protein kinase (AMPK) serves as a crucial energy sensor, maintaining organismal energy homeostasis through the regulation of diverse metabolic pathways. However, the association between the AMPK signaling pathway and hypoxia adaptation in yak lung tissue has not yet been elucidated. Consequently, this study focused on the lung tissues of yaks and cattle residing at the same altitude (2600 m). Morphological analysis demonstrated that, compared to cattle, yak lung tissue possessed significantly thicker alveolar septa (P < 0.05), a greater abundance of elastic fibers (P < 0.05), and a reduced blood-air barrier thickness (P < 0.05), suggesting substantial structural adaptations in the yak lung under identical altitudinal conditions. RNA-seq analysis identified 3684 genes with significant differential expression between yaks and cattle. KEGG pathway enrichment analysis showed significant enrichment for the AMPK signaling pathway under the "Environmental Information Processing" category, and Gene Set Enrichment Analysis (GSEA) further confirmed the activation of the AMPK signaling pathway in yak lung tissue. Despite qRT-PCR indicating reduced mRNA levels of key AMPK pathway genes (PRKAA1, PRKAA2, PRKAB1, PRKAG2) in yak lung tissue, Western blot analysis demonstrated a marked upregulation in the relative abundance of phosphorylated AMPK (P-AMPK α1 + α2), implying potential activation of the AMPK signaling pathway via phosphorylation in yak lung tissue. Further analysis of downstream gene expression within the AMPK signaling pathway indicated significant downregulation of genes associated with glucose metabolism (PCK2, G6PC1), lipid metabolism (FASN, ACACA), protein metabolism (MAPKAPK5, MTOR), cell proliferation and apoptosis (RPTOR, MTOR), and autophagy (TXNIP, NLRP3) in yak lung tissue. These findings suggest that, relative to cattle, the yak lung may adapt to hypoxic conditions by minimizing energy expenditure, suppressing aberrant cell proliferation, mitigating oxidative stress, and reducing inflammatory responses. In summary, the activation of the AMPK signaling pathway in yak lung tissue may play a crucial role in hypoxic adaptation by enhancing oxygen utilization and energy supply capacity.