Regulation of muscle pyruvate dehydrogenase activity and exercise fuel use in high-altitude deer mice
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abstract
Adult, lab-reared, highland deer mice acclimate to hypoxia by increasing reliance on carbohydrates to fuel exercise. Yet neither the underlying mechanisms for this shift in fuel use pattern, nor the impact of lifetime hypoxia exposure experienced in the high alpine, are fully understood. Thus, we assessed exercise fuel use in wild highland deer mice running in their native environment. We examined a key step in muscle carbohydrate oxidation, pyruvate dehydrogenase (PDH) and its regulation with exercise at altitude in wild highlanders and using first generation (G1) lab born and raised highlanders acclimated to normoxia or hypoxia. PDH activity was also determined in the gastrocnemius of G1 highlanders using an in situ muscle preparation. We found wild highlanders had a high reliance on carbohydrates while running in their native environment, consistent with data from hypoxia acclimated G1 highlanders. PDH activity in the gastrocnemius was similar post exercise between G1 and wild highlanders. However, when the gastrocnemius was stimulated at a light work rate in situ, PDH activity was higher in hypoxia acclimated G1 highlanders, and associated with a lower intramuscular lactate. These findings were supported by lower PDH kinase 2 protein expression in hypoxia acclimated G1 mice. Our findings indicate that adult phenotypic plasticity in response to low oxygen is sufficient to increase exercise carbohydrate reliance in highland deer mice. Additionally, variation in PDH regulation with hypoxia acclimation contributes to shifts in whole-animal fuel use patterns and are likely to improved exercise performance via elevated energy yield per mole O2.
