Regulatory Role of Adrenomedullin in Hypoxic Adaptation of Yak Subcutaneous Preadipocytes.

High-altitude hypoxic environments constrain yaks' survival capacity and metabolic adaptability. Subcutaneous adipose tissue helps yaks withstand cold and resist hypoxic stress, and ADM participates in cellular stress and metabolic regulation. To explore the regulatory role of ADM in the hypoxia adaptation of yak subcutaneous preadipocytes in high-altitude environments, we established three cell culture groups (normoxia, physiological hypoxia, and hypoxia). We further systematically examined cell proliferation, apoptosis, adenosine triphosphate (ATP) production, and lipid metabolic markers, and we performed transcriptome sequencing to reveal their regulatory effects. ADM exhibited a bidirectional regulatory effect: Low doses alleviated hypoxia-induced cell damage and restored energy and lipid synthesis, whereas high doses, in conjunction with hypoxia, activated multiple metabolic pathways and altered cellular energy-supply patterns. Under physiological hypoxia, cells emphasized metabolic regulation, while under hypoxia, they prioritized stress defense. This study demonstrates that under hypoxic stress, ADM regulates the survival and physiological function of yak subcutaneous preadipocytes in a dose-dependent manner, with cells relying on staged stress-defense and metabolic-remodeling responses to achieve adaptation to hypoxia, providing important experimental and theoretical insights into the mechanisms of high-altitude hypoxia adaptation in yaks.