Transcriptomic plasticity in brown adipose tissue contributes to an enhanced capacity for nonshivering thermogenesis...

For small mammals living at high altitude, aerobic heat generation (thermogenesis) is essential for survival during prolonged periods of cold, but is severely impaired under conditions of hypobaric hypoxia. Recent studies in deer mice (Peromyscus maniculatus) reveal adaptive enhancement of thermogenesis in high- compared to low-altitude populations under hypoxic cold stress, an enhancement that is attributable to modifications in the aerobic metabolism of muscles used in shivering. However, because small mammals rely heavily on nonshivering mechanisms for cold acclimatization, we tested for evidence of adaptive divergence in nonshivering thermogenesis (NST) under hypoxia. To do so, we measured NST and characterized transcriptional profiles of brown adipose tissue (BAT) in high- and low-altitude deer mice that were (i) wild-caught and acclimatized to their native altitude, and (ii) born and reared under common garden conditions at low elevation. We found that NST performance under hypoxia is enhanced in wild-caught, high-altitude deer mice, a difference that is associated with increased expression of coregulated genes that influence several physiological traits. These traits include vascularization and O2 supply to BAT, brown adipocyte proliferation and the uncoupling of oxidative phosphorylation from ATP synthesis in the generation of heat. Our results suggest that acclimatization to hypoxic cold stress is facilitated by enhancement of nonshivering heat production, which is driven by regulatory plasticity in a suite of genes that influence intersecting physiological pathways.