Exercise training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic capacity

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2011-01, Vol.300 (1), p.R175-R182
• Main Authors: Lessard, Sarah J, Rivas, Donato A, Stephenson, Erin J, Yaspelkis, 3rd, Ben B, Koch, Lauren G, Britton, Steven L, Hawley, John A
• Format: Article
• Language: English
• Subjects: Animals; Carbohydrate Metabolism - genetics; Carbohydrate Metabolism - physiology; Exercise; Genetics; Lipid Metabolism - genetics; Lipid Metabolism - physiology; Lipids; Metabolism; Models, Animal; Muscle, Skeletal - metabolism; Musculoskeletal system; Nuclear Receptor Subfamily 4, Group A, Member 1 - physiology; Physical Conditioning, Animal - physiology; Physical Endurance - genetics; Physical Endurance - physiology; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta - physiology; Signal Transduction - physiology; Tissues
• ISSN: 0363-6119; 1522-1490; 1522-1490
• DOI: 10.1152/ajpregu.00338.2010

We have used a novel model of genetically imparted endurance exercise capacity and metabolic health to study the genetic and environmental contributions to skeletal muscle glucose and lipid metabolism. We hypothesized that metabolic abnormalities associated with low intrinsic running capacity would be ameliorated by exercise training. Selective breeding for 22 generations resulted in rat models with a fivefold difference in intrinsic aerobic capacity. Low (LCR)- and high (HCR)-capacity runners remained sedentary (SED) or underwent 6 wk of exercise training (EXT). Insulin-stimulated glucose transport, insulin signal transduction, and rates of palmitate oxidation were lower in LCR SED vs. HCR SED (P < 0.05). Decreases in glucose and lipid metabolism were associated with decreased β₂-adrenergic receptor (β₂-AR), and reduced expression of Nur77 target proteins that are critical regulators of muscle glucose and lipid metabolism [uncoupling protein-3 (UCP3), fatty acid transporter (FAT)/CD36; P < 0.01 and P < 0.05, respectively]. EXT reversed the impairments to glucose and lipid metabolism observed in the skeletal muscle of LCR, while increasing the expression of β₂-AR, Nur77, GLUT4, UCP3, and FAT/CD36 (P < 0.05) in this tissue. However, no metabolic improvements were observed following exercise training in HCR. Our results demonstrate that metabolic impairments resulting from genetic factors (low intrinsic aerobic capacity) can be overcome by an environmental intervention (exercise training). Furthermore, we identify Nur77 as a potential mechanism for improved skeletal muscle metabolism in response to EXT.