Physiological and Morphometric Differences in Resident Moderate-Altitude vs. Sea-Level Mice

INTRODUCTION: High-altitude [>2400 m (7874 ft)] acclimatization has been well studied with physiological adaptations like reductions in body weight and exercise capacity. However, despite the significance of moderate altitude [MA, 1524-2438 m (5000-8000 ft)], acclimatization at this elevation is not well described. We aimed to investigate differences in mice reared at MA compared to sea level (SL). We hypothesized that MA mice would be smaller and leaner and voluntarily run less than SL mice.METHODS: C57BL/6 mice reared for at least three generations in Laramie, WY [2194 m (7198 ft), MA], were compared to C57BL/6J mice from Bar Harbor, ME [20 m (66 ft), SL]. We quantified body composition and exercise outputs as well as cardiopulmonary morphometrics. Subsets of MA and SL mice were analyzed to determine differences in neuronal activation after exercise.RESULTS: When body weight was normalized to tibia length, SL animals weighed 1.30 g ⋅ mm^-1 while MA mice weighed 1.13 g · mm^-1. Total fat % and trunk fat % were higher in MA mice with values of 41% and 39%, respectively, compared to SL mice with values of 28% and 26%, respectively. However, no differences were noted in leg fat %. MA animals had higher heart mass (119 mg) and lower lung mass (160 mg) compared to SL mice heart mass (100 mg) and lung mass (177 mg). MA mice engaged in about 40% less voluntary wheel-running activity than SL animals.DISCUSSION: Physiological differences are apparent between MA and SL mice, prompting a need to further understand larger scale implications of residence at moderate altitude.O'Connor AE, Hatzenbiler DM, Flom LT, Bobadilla A-C, Bruns DR, Schmitt EE.