Low-intensity exercise induces acute shifts in liver and skeletal muscle substrate metabolism, but not chronic adaptations in tissue oxidative capacity.

Abstract

Adaptations in hepatic and skeletal muscle substrate metabolism following acute and chronic (6 weeks; 5 days/week; 1 h/day) low-intensity treadmill exercise were tested in healthy male C57BL/6J mice. Low-intensity exercise maximizes lipid utilization; therefore, we hypothesized pathways involved in lipid metabolism would be most robustly affected. Acute exercise nearly depleted liver glycogen immediately post-exercise (0h), while hepatic triglyceride (TAG) stores increased in the early stages after exercise (0-3h). Also, hepatic Pgc-1a gene expression and fat oxidation (mitochondrial and peroxisomal) increased immediately post-exercise (0h), whereas carbohydrate and amino acid oxidation in liver peaked 24-48h later. Alternatively, skeletal muscle exhibited a less robust response to acute exercise as stored substrates (glycogen and TAG) remained unchanged, induction of Pgc-1a gene expression was delayed (up at 3h), and mitochondrial substrate oxidation pathways (carbohydrate, amino acid and lipid) were largely unaltered. Peroxisomal lipid oxidation exhibited the most dynamic changes in skeletal muscle substrate metabolism after acute exercise; however, this response was also delayed (peaked 3-24h post-exercise) and expression of peroxisomal genes remained unaffected. Interestingly, 6 weeks of training at a similar intensity limited weight gain, increased muscle glycogen, and reduced TAG accrual in liver and muscle; however, substrate oxidation pathways remained unaltered in both tissues. Collectively these results suggest changes in substrate metabolism induced by an acute low-intensity exercise bout in healthy mice are more rapid and robust in liver than in skeletal muscle; however, training at a similar intensity for 6 weeks is insufficient to induce remodeling of substrate metabolism pathways in either tissue.