Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats.

Sean M Garvey,Mary B Skelding,Neile K Edens,Janis E Dugle,David W Russ

doi:10.14814/phy2.12319

Abstract

We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16–17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW−). The 9 RW+ rats averaged 83 m/day (range: 8–163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW− rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle.

Highlights

Because of increasing sedentarism and overall age of western populations, it is of critical importance to identify lifestyle interventions from early to late middle age to lessen the negative consequences of inactivity and aging
We found that 8 weeks of running wheel (RW) activity significantly decreased body weight gain compared to rats without RW access (Fig. 3), there were no significant effects on the weights of several hindlimb muscles (Table 1)
Consistent with enhanced beta-oxidation of lipids, RW activity was associated with a fasting intramuscular metabolomic signature comprising decreased abundance of long-chain fatty acids (LCFAs)

Summary

Introduction

Because of increasing sedentarism and overall age of western populations, it is of critical importance to identify lifestyle interventions from early to late middle age to lessen the negative consequences of inactivity and aging Both caloric restriction and physical activity have been shown to promote longevity and healthspan, significant controversy persists over the longevity-associated effects of caloric restriction in primates (Colman et al 2009; Mattison et al 2012). Observational studies have shown that lower BMI (< 23 kg/m2) is associated with higher risk of mortality in elderly subjects (Winter et al 2014), and that overweight subjects (BMI of 25 –

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