FUEL USE AND METABOLIC ADAPTATIONS TO HIGH ALTITUDE IN SMALL MAMMALS

Abstract

<p>Knowledge on fuel use and muscle metabolism in high altitude mammals is very limited. Yet, as the oxidation of carbohydrates offers an oxygen-saving advantage over the oxidation of fatty acids (15-30% more energy produced per oxygen used), one possible adaptation to maintain performance at high altitude is to elevate the use of carbohydrates as a fuel source for energy metabolism. To test this hypothesis, I performed intraspecific and interspecific comparisons of whole-body fuel use and muscle metabolism in closely related high (4000-4500 m) and low altitude (100-300 m) native mice (genus <em>Phyllotis</em>), which I collected at different locations in Andean and coastal regions of Peru. My results show a higher proportional use of carbohydrates when oxygen becomes limited in high altitude <em>Phyllotis</em> in comparison to their low altitude counterparts. This phenotype does not seem to result from similar phylogenetic history or from a chronic exposure to hypobaric hypoxia during development or adulthood. Accordingly, this thesis provides the first compelling evidence of enhanced carbohydrate utilization as an adaptation to high altitude, a hypothesis proposed nearly 30 years ago. The mechanisms responsible for this shift in fuel use are unknown. There were no strong indications of a greater capacity for carbohydrate oxidation in skeletal and cardiac muscles of high altitude <em>Phyllotis</em> mice. Finally, as this thesis provides the first report of whole-body fuel use in mice, a comparison with other mammalian species (rats, dogs and goats) revealed that the current model of mammalian fuel selection, which is thought to be conserved among mammals, does not apply to small mammals. I thus revisited the current model and proposed a new one general to all mammals. This thesis thus provides significant advancements not only in the field of high altitude physiology but also in the field of mammalian energetics.</p>