Diversity in the regulation of metabolic fuel use in mice selected for high locomotor activity

Abstract

<p>Despite diversity in locomotion, the mammalian pattern of metabolic fuel use appears highly conserved, and in most circumstances relative exercise intensity dictates the proportionate contribution of carbohydrates and lipids to energy supply. However, the mechanistic explanations for unity of fuel use patterns are not known. The aim of my study was to determine if fuel use during exercise could be adaptively altered or differentially regulated in animals selected for high activity.</p> <p>To thi s end, I used a model of experimental evolution in which mice are selectively bred for high locomotion. Within this model, there are two distinct phenotypes of high running (HR) mice: HR_mini mice, characterized by half-sized hindlimb muscles with increased mass-specific aerobic capacity, and HR_normal mice, with a normal muscle phenotype. I evaluated aerobic capacity (VO_2max), fuel use during exercise, cardiac properties, and physiological factors involved in regulating fuel use, in one line each of: 1) non-selected control mice, 2) HR_mini mice, and 3) HR_normal mice.</p> <p>HR mice exhibited an increased VO_2max compared to controls; moreover, HR_mini mice had a greater VO_2max than HR_normal mice. Metabolic and physical cardiac changes may have contributed to these VO_2max differences. However, HR_mini, HR_normal, and control mice did not differ in the mixture of fuels supplying energy demand, when exercise intensity was scaled to VO_2max. HR mice achieved enhanced absolute fuel oxidation rates via different means. HR_mini mice had increased cytosolic fatty acid binding protein (H-FABP), fatty acid transporter (FAT/CD36) mRNA, peroxisome proliferator-activated receptor (PPAR) α mRNA, and activities of aerobic enzymes in skeletal muscle, as well as a different muscle recruitment pattern. Conversely, HR_normal mice had enhanced whole-muscle enzyme activities. Therefore, there are multiple mechanisms to enhance fuel oxidation rates with an elevated VO_2max, and diverse mammals can differentially utilize these mechanisms without deviating from a conserved pattern of fuel use.</p>