High‐Altitude Adaptation of Frogs (Case Study: <i>Nanorana parkeri</i> ): From Physiological Phenotypes to AltitudeOmics

High altitudes are challenging for the animals that inhabit these environments. The Xizang plateau frog (Nanorana parkeri), endemic to the Qinghai-Tibet Plateau and distributed between 2800 and 5100 m, represents an ideal model for studying high-altitude adaptations. Here, we compared environmental differences between high- (4600 m) and low-altitude (3400 m) habitats, characterized the physiological traits of high-altitude frogs, and integrated metabolomic and proteomic data to elucidate adaptive mechanisms to extreme environments. High-altitude habitats exhibited significantly lower water temperatures and dissolved oxygen levels. High-altitude frogs showed a 31%-37% reduction in resting metabolic rate, decreased concentrations of metabolites (glucose and β-hydroxybutyric acid), and 18%-56% lower activities of critical metabolic enzymes. This coordinated metabolic depression is indicative of an energy conservation strategy for surviving at high altitudes. Interestingly, hepatic glycogen (3.1-fold increase) and pyruvate accumulated in high-altitude frogs, suggesting enhanced energy storage and potential antioxidant utilization. Metabolomic profiling further revealed a remodeling of glycerophospholipid, indicating adaptive membrane stabilization. Proteomics analysis identified altered expression of proteins involved in stress response, energy metabolism, and translation, including chaperones (DNAJB6 and DNAJC22) and glutathione peroxidase (GPX4), which may be potential biomarkers for evaluating high-altitude adaptation in ectothermic vertebrates. Collectively, these findings demonstrate that N. parkeri survives in high-altitude environments through a synergistic strategy of metabolic remodeling and protein expression adjustment to optimize energy efficiency and enhance cellular protection. This study provides new insights into the mechanisms by which ectothermic vertebrates adapt to extreme environments.