Selective breeding of mice for high voluntary exercise alters adaptive plasticity of metabolic phenotypes in skeletal muscle

Abstract

The response to selection on behavior necessarily entails associated changes in lower‐level (subordinate) traits. We studied mice from 4 replicate lines that had been selectively bred for high levels of voluntary exercise (High Runner or HR) that run ~3‐fold more wheel revolutions/day than those from 4 non‐selected control (C) lines, and have evolved higher baseline endurance and VO2max. We examined hindlimb skeletal muscle metabolic capacity in mice housed with or without wheel access for 8 weeks. Triceps surae muscles were assayed at 37C for Vmax of hexokinase (HK), citrate synthase (CS), carnitine palmitoyl‐transferase (CPT), and β‐hydroxyacyl‐CoA dehydrogenase (HAD). Wheel access increased heart ventricle mass in both HR and C lines, but only HR showed increased enzyme activities as well as higher phosphorylation of 5ˈ‐AMP‐activated protein kinase. Analysis of wheel‐access groups indicated the greater training effect in HR could be explained statistically by their greater wheel running for ventricle mass, CS, and HAD, but for HK and CPT, HR mice had greater adaptive plasticity of the response to voluntary exercise. Thus, HR do not have inherent baseline differences in metabolic capacity, but they have evolved greater adaptive plasticity for some traits. Supported by NSF IOB‐0543429 and IOS‐1121273 to TG.