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Exercise is an important performance trait in mammals and variation in aerobic capacity and/or substrate allocation during submaximal exercise may be important for survival at high altitude. Comparisons between lowland and highland populations is a fruitful approach to understanding the mechanisms for altitude differences in exercise performance. However, it has only been applied in very few highland species. The leaf-eared mice (LEM, genus Phyllotis ) of South America are a promising taxon to uncover the pervasiveness of hypoxia tolerance mechanisms. Here we use lowland and highland populations of Andean and Lima LEM ( P. andium and P. limatus ), acclimated to common laboratory conditions, to determine exercise-induced maximal oxygen consumption (V˙O 2 max), and submaximal exercise metabolism. Lowland and highland populations of both species showed no difference in V˙O 2 max running in either normoxia or hypoxia. When run at 75% of V˙O 2 max, highland Andean LEM had a greater reliance on carbohydrate oxidation to power exercise. In contrast, highland Lima LEM showed no difference in exercise fuel use compared to their lowland counterparts. The higher carbohydrate oxidation seen in highland Andean LEM was not explained by maximal activities of glycolytic enzymes in the gastrocnemius muscle, which were equivalent to lowlanders. This result is consistent with data on highland deer mouse populations and suggests changes in metabolic regulation may explain altitude differences in exercise performance.

Fuel selection patterns during exercise are thought to be conserved among sea-level native mammals when intensity is expressed relative to maximum aerobic capacity (V̇(O₂,max)). However, this claim is based on data from only a few species larger than rats, and has never been tested statistically. Thus, we investigated fuel use in a small mammal (Mus musculus, CD-1 strain), and combined these data with published data on rats, dogs, goats and humans to evaluate the robustness of the mammalian fuel selection model. We found that mice rely less on carbohydrates to power moderate intensity exercise at the same % V̇(O₂,max) than larger mammals. We suggest that this difference is due to a decline in aerobic scope (O2 available for exercise above resting metabolism) as body size decreases. We propose a redefined fuel use model that reflects changes in fractional aerobic scope with body size. Our results indicate that exercise defined as percent aerobic scope is a better predictor of fuel use across a wide range of quadruped species from mice to dogs and running humans., (© 2014. Published by The Company of Biologists Ltd.)

The low oxygen levels at high altitude are a potent and unavoidable physiological stressor to which highland mammals must adapt. One hypothesized adaptation to high altitude is an increased reliance on carbohydrates to support aerobic activities. Based on stoichiometries of combustion, ATP yield per mole of oxygen from carbohydrates is approximately 15% higher than from lipids (observed difference closer to 30%), and increased carbohydrate use represents an important oxygen-saving strategy that may be under high selective pressure. Although this hypothesis was first proposed nearly 30 years ago, the in vivo patterns of whole-body fuel use during exercise remain undefined for any highland mammal (including humans). Here we use a powerful multispecies approach to show that wild-caught high-altitude (4,000-4,500 m) native species of mice (Phyllotis andium and Phyllotis xanthopygus) from the Peruvian Andes use proportionately more carbohydrates and have higher oxidative capacities of cardiac muscles compared to closely related low-altitude (100-300 m) native counterparts (Phyllotis amicus and Phyllotis limatus). These results strongly infer that highland Phyllotis have evolved a metabolic strategy to economize oxygen when performing energy-demanding tasks at altitude. This study provides compelling evidence of adjustments in fuel use as an adaptation to high-altitude hypoxia in mammals., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Honeybees, Apis mellifera, who show temporal polyethism, begin their adult life performing tasks inside the hive (hive bees) and then switch to foraging when they are about 2-3 weeks old (foragers). Usually hive tasks require little or no flying, whereas foraging involves flying for several hours a day and carrying heavy loads of nectar and pollen. Flight muscles are particularly plastic organs that can respond to use and disuse, and accordingly it would be expected that adjustments in flight muscle metabolism occur throughout a bee's life. We thus investigated changes in lifetime flight metabolic rate and flight muscle biochemistry of differently aged hive bees and of foragers with varying foraging experience. Rapid increases in flight metabolic rates early in life coincided with a switch in troponin T isoforms and increases in flight muscle maximal activities (V (max)) of the enzymes citrate synthase, cytochrome c oxidase, hexokinase, phosphofructokinase, and pyruvate kinase. However, further increases in flight metabolic rate in experienced foragers occurred without additional changes in the in vitro V (max) of these flight muscle metabolic enzymes. Estimates of in vivo flux (v) compared to maximum flux of each enzyme in vitro (fractional velocity, v/V (max)) suggest that most enzymes operate at a higher fraction of V (max) in mature foragers compared to young hive bees. Our results indicate that honeybees develop most of their flight muscle metabolic machinery early in life. Any further increases in flight metabolism with age or foraging experience are most likely achieved by operating metabolic enzymes closer to their maximal flux capacity.

Honeybees, Apis mellifera, gradually increase their rate of forage uptake as they gain foraging experience. This increase in foraging performance has been proposed to occur as a result of learning; however, factors affecting flight ability such as changes in physiological components of flight metabolism could also contribute to this pattern. Thus, the purpose of this study was to assess the contribution of physiological changes to the increase in honeybee foraging performance. We investigated aspects of honeybee flight muscle biochemistry throughout the adult life, from non-foraging hive bees, through young and mature foragers, to old foragers near the end of their lifespan. Two-dimensional gel proteomic analysis on honeybee thorax muscle revealed an increase in several proteins from hive bees to mature foragers including troponin T 10a, aldolase and superoxide dismutase. By contrast, the activities (V(max)) of enzymes involved in aerobic performance, phosphofructokinase, hexokinase, pyruvate kinase and cytochrome c oxidase, did not increase in the flight muscles of hive bees, young foragers, mature foragers and old foragers. However, citrate synthase activity was found to increase with foraging experience. Hence, our results suggest plasticity in both structural and metabolic components of flight muscles with foraging experience.