Spargo FJ, McGee SL, Dzamko N, Watt MJ, Kemp BE, Britton SL, Koch LG, Hargreaves M, Hawley JA. Dysregulation of muscle lipid metabolism in rats selectively bred for low aerobic running capacity. Am J Physiol Endocrinol Metab 292: E1631-E1636, 2007. First published February 6, 2007 doi:10.1152/ajpendo.00702.2006.-As substrate for evaluation of metabolic diseases, we developed novel rat models that contrast for endurance exercise capacity. Through twoway artificial selection, we created rodent phenotypes of intrinsically low-capacity runners (LCR) and high-capacity runners (HCR) that also differed markedly for cardiovascular and metabolic disease risk factors. Here, we determined skeletal muscle proteins with putative roles in lipid and carbohydrate metabolism to better understand the mechanisms underlying differences in whole body substrate handling between phenotypes. Animals (generation 16) differed for endurance running capacity by 295%. LCR animals had higher resting plasma glucose (6.58 Ϯ 0.45 vs. 6.09 Ϯ 0.45 mmol/l), insulin (0.48 Ϯ 0.03 vs. 0.32 Ϯ 0.02 ng/ml), nonesterified fatty acid (0.57 Ϯ 0.14 v 0.35 Ϯ 0.05 mM), and triglyceride (TG; 0.47 Ϯ 0.11 vs. 0.25 Ϯ 0.08 mmol/l) concentrations (all P Ͻ 0.05). Muscle TG (72.3 Ϯ 14.7 vs. 38.9 Ϯ 6.2 mmol/kg dry muscle wt; P Ͻ 0.05) and diacylglycerol (96 Ϯ 28 vs. 42 Ϯ 8 pmol/mg dry muscle wt; P Ͻ 0.05) contents were elevated in LCR vs. HCR rats. Accompanying the greater lipid accretion in LCR was increased fatty acid translocase/CD36 content (1,014 Ϯ 80 vs. 781 Ϯ 70 arbitrary units; P Ͻ 0.05) and reduced TG lipase activity (0.158 Ϯ 0.0125 vs. 0.274 Ϯ 0.018 mmol⅐min Ϫ1 ⅐kg dry muscle wt Ϫ1 ; P Ͻ 0.05). Muscle glycogen, GLUT4 protein, and basal phosphorylation states of AMP-activated protein kinase-␣1, AMP-activated protein kinase-␣2, and acetyl-CoA carboxylase were similar in LCR and HCR. In conclusion, rats with low intrinsic aerobic capacity demonstrate abnormalities in lipid-handling capacity. These disruptions may, in part, be responsible for the increased risk of metabolic disorders observed in this phenotype. exercise capacity; insulin resistance; mitochondrial biogenesis; lipids DURING THE PAST 50 YEARS, the prevalence of a cluster of interrelated chronic metabolic disease states including coronary heart disease, insulin resistance, type 2 diabetes mellitus, and obesity has reached epidemic proportions (5). The etiological basis of these disorders is both polygenic and dependent on environmental factors. However, because no new major human gene mutations have occurred in the latter half of the 20th century to cause this greater frequency of chronic metabolic diseases, the increased incidence must principally be due to alterations in environmental conditions. One contemporary environmental factor that changed and is strongly associated with chronic metabolic disorders is the decline in physical activity (8). Indeed, the increased prevalence of coronary heart disease, insulin resistance, type 2 diabetes mellitus, and obesity and their strong associations with i...

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During the past 30 years, considerable progress has been made in our understanding of the cellular and molecular factors regulating fuel metabolism during exercise. In particular, advancements in the fields of exercise biochemistry and cell signalling have helped elucidate the mechanism(s) by which perturbations in energy status are monitored inside contracting muscle cells, and have helped identify target molecules that increase fuel supply to maintain adenosine triphosphate concentration. In this brief commentary, we summarise some of the major cellular and molecular adaptations in human skeletal muscle resulting from the intense endurance training required to run a marathon.

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