Abstract
Adaptations in hepatic and skeletal muscle substrate metabolism following acute and chronic (6 wk; 5 days/wk; 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 postexercise (0 h), whereas hepatic triglyceride (TAG) stores increased in the early stages after exercise (0-3 h). Also, hepatic peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene expression and fat oxidation (mitochondrial and peroxisomal) increased immediately postexercise (0 h), whereas carbohydrate and amino acid oxidation in liver peaked 24-48 h later. Alternatively, skeletal muscle exhibited a less robust response to acute exercise as stored substrates (glycogen and TAG) remained unchanged, induction of PGC-1α gene expression was delayed (up at 3 h), 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 3-24 h postexercise), and expression of peroxisomal genes remained unaffected. Interestingly, 6 wk 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 wk is insufficient to induce remodeling of substrate metabolism pathways in either tissue. NEW & NOTEWORTHY Effects of low-intensity exercise on substrate metabolism pathways were tested in liver and skeletal muscle of healthy mice. This is the first study to describe exercise-induced adaptations in peroxisomal lipid metabolism and also reports comprehensive adaptations in mitochondrial substrate metabolism pathways (carbohydrate, lipid, and amino acid). Acute low-intensity exercise induced shifts in mitochondrial and peroxisomal metabolism in both tissues, but training at this intensity did not induce adaptive remodeling of metabolic pathways in healthy mice.
Highlights
Substrate preference during exercise varies with intensity
We were interested in testing adaptations in lipid metabolism, so low-intensity exercise was chosen because 1) lipid is the primary fuel used at this intensity and 2) it emphasizes the contribution of circulating fuels to meet the increased energy demand of skeletal muscle
Postexercise (0 h), the expected increase in circulating nonesterified fatty acids (NEFAs) was observed (Fig. 1C); there were no changes in circulating triglycerides (TAGs; Fig. 1D) and only a slight decrease in glucose (Fig. 1E)
Summary
Substrate preference during exercise varies with intensity. At low intensities [Ͻ40% maximal oxygen consumption (V O2max)] lipid is the predominant fuel, and as intensity increases the body starts to rely more heavily on carbohydrates [7, 8, 10, 30, 61]. Peak fat oxidation rates are achieved at submaximal exercise (approximately 45– 65% peak oxygen consumption), but as intensity increases above this point reliance on lipid diminishes and glucose becomes the predominant fuel, a phenomenon referred to as the crossover concept [7,8,9, 24, 59, 60]. During low-intensity exercise, skeletal muscle utilizes a greater percentage of these circulating substrates; as intensity increases, there is greater reliance on intramuscular triglyceride and glycogen stores [61]. These findings emphasize that substrate mobilization and metabolism must be coordinated among multiple organ systems in response to exercise; understanding these relationships is important to maximize the health benefits. The interaction between skeletal muscle and liver is of particular interest
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