title: High Intrinsic Aerobic Capacity Protects against Ethanol-Induced Hepatic Injury and Metabolic Dysfunction: Study Using High Capacity Runner Rat Model.
abstract: Rats artificially selected over several generations for high intrinsic endurance/aerobic capacity resulting in high capacity runners (HCR) has been developed to study the links between high aerobic fitness and protection from metabolic diseases (Wisloff et al., Science, 2005). We have previously shown that the HCR strain have elevated hepatic mitochondrial content and oxidative capacity. In this study, we tested if the elevated hepatic mitochondrial content in the HCR rat would provide "metabolic protection" from chronic ethanol-induced hepatic steatosis and injury. The Leiber-Decarli liquid diet with ethanol (7% v/v; HCR-E) and without (HCR-C) was given to HCR rats (n = 8 per group) from 14 to 20 weeks of age that were weight matched and pair-fed to assure isocaloric intake. Hepatic triglyceride (TG) content and macro- and microvesicular steatosis were significantly greater in HCR-E compared with HCR-C (p < 0.05). In addition, hepatic superoxide dismutase activity and glutathione levels were significantly (p < 0.05) reduced in the HCR-E rats. This hepatic phenotype also was associated with reduced total hepatic fatty acid oxidation (p = 0.03) and β-hydroxyacyl-CoA dehydrogenase activity (p = 0.01), and reductions in microsomal triglyceride transfer protein and apoB-100 protein content (p = 0.01) in HCR-E animals. However, despite these documented hepatic alterations, ethanol ingestion failed to induce significant hepatic liver injury, including no changes in hepatic inflammation, or serum alanine amino transferase (ALTs), free fatty acids (FFAs), triglycerides (TGs), insulin, or glucose. High intrinsic aerobic fitness did not reduce ethanol-induced hepatic steatosis, but protected against ethanol-induced hepatic injury and systemic metabolic dysfunction in a high aerobic capacity rat model.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO 65212, USA. nms.20007@gmail.com.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Szary
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO 65212, USA. RectorS@health.missouri.edu.|Harry S. Truman Memorial Veterans Medical Center, 800 Hospital Drive, Columbia, MO 65201, USA. RectorS@health.missouri.edu.|Departments of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, USA. RectorS@health.missouri.edu.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO 65212, USA. meersg@health.missouri.edu.|Harry S. Truman Memorial Veterans Medical Center, 800 Hospital Drive, Columbia, MO 65201, USA. meersg@health.missouri.edu.
authors.forename: Grace M
authors.initials: GM
authors.lastname: Uptergrove
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO 65212, USA. ridenhoursuz@health.missouri.edu.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Ridenhour
authors.affiliation: Departments of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA. shuklasd@missouri.edu.
authors.forename: Shivendra D
authors.initials: SD
authors.lastname: Shukla
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO 65212, USA. jthyfault@kumc.edu.|Harry S. Truman Memorial Veterans Medical Center, 800 Hospital Drive, Columbia, MO 65201, USA. jthyfault@kumc.edu.|Departments of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, USA. jthyfault@kumc.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.affiliation: Departments of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA. lgkoch@umich.edu.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Departments of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA. brittons@umich.edu.|Departments of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA. brittons@umich.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO 65212, USA. ibdahj@health.missouri.edu.|Harry S. Truman Memorial Veterans Medical Center, 800 Hospital Drive, Columbia, MO 65201, USA. ibdahj@health.missouri.edu.|Departments of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, USA. ibdahj@health.missouri.edu.|Departments of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA. ibdahj@health.missouri.edu.
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000378:metabolism / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism / Q000517:prevention & control*; D008930:Mitochondria, Liver / Q000378:metabolism; D005082:Physical Exertion; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D053299:Apolipoprotein B-100; D001786:Blood Glucose; D014280:Triglycerides; D015094:3-Hydroxyacyl CoA Dehydrogenases; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: aerobic fitness; ethanol; fatty liver disease; mitochondrial function