Abstract

We examined the molecular and metabolomic effects of low‐intensity exercise in late middle‐aged male Sprague Dawley rats (16‐17 months). Animals were assigned either continuous running wheel access for 8 weeks (RW+) or cage‐matched without running wheels (RW‐). The 9 RW+ rats averaged just 83 m/day (range: 8‐163 m), yet exhibited 6% reduced individual average weekly food intake (145 g vs 154 g, p<0.01) and 84% reduced individual body weight gain (4.3 g vs 26.3 g, p=0.02) over the 8 weeks. Muscle weights and myofiber area showed no difference between groups. Western blots of gastrocnemius lysates with a panel of antibodies suggest that running wheel access improved oxidative metabolism (53% increase in PGC1‐α, p=0.02), increased autophagy (36% increase in LC3B‐II:‐I ratio; p=0.03), and modulated growth signaling (26% increase in myostatin, p=0.04). RW+ gastrocnemius lysates also showed 45% increased glycogen content (p=0.04) and 43% increased glycogen phosphorylase expression (p=0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low‐volume voluntary wheel running is associated with decreases in many long chain fatty acids (e.g., palmitoleate, myristoleate) relative to RW‐ rats. Increases in acylcarnitines and glycerophosphocholines were more specific to plantaris. These data further establish extensive metabolic and behavioral remodeling due to small amounts of exercise.

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