Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury

John P. Thyfault; R. Scott Rector; Grace M. Uptergrove; Sarah J. Borengasser; E. Matthew Morris; Yongzhong Wei; Matt J. Laye; Charles F. Burant; Nathan R. Qi; Suzanne E. Ridenhour; Lauren G. Koch; Steve L. Britton; Jamal A. Ibdah

doi:10.1113/jphysiol.2009.169060

journal article Apr 14, 2009

Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury

John P. Thyfault R. Scott Rector Grace M. Uptergrove Sarah J. Borengasser E. Matthew Morris

Yongzhong Wei Matt J. Laye Charles F. Burant

Nathan R. Qi Suzanne E. Ridenhour Lauren G. Koch

Steve L. Britton Jamal A. Ibdah

The Journal of Physiology Vol. 587 No. 8 pp. 1805-1816 · Wiley

View at Publisher Save 10.1113/jphysiol.2009.169060

Abstract

Fatty liver has been linked to low aerobic fitness, but the mechanisms are unknown. We previously reported a novel model in which rats were artificially selected to be high capacity runners (HCR) and low capacity runners (LCR) that in a sedentary condition have robustly different intrinsic aerobic capacities. We utilized sedentary HCR/LCR rats (generation 17; max running distance equalled 1514 ± 91 vs. 200 ± 12 m for HCR and LCR, respectively) to investigate if low aerobic capacity is associated with reduced hepatic mitochondrial oxidative capacity and increased susceptibility to hepatic steatosis. At 25 weeks of age, LCR livers displayed reduced mitochondrial content (reduced citrate synthase activity and cytochrome c protein) and reduced oxidative capacity (complete palmitate oxidation in hepatic mitochondria (1.15 ± 0.13 vs. 2.48 ± 1.1 nm g−1 h, P < 0.0001) and increased peroxisomal activity (acyl CoA oxidase and catalase activity) compared to the HCR. The LCR livers also displayed a lipogenic phenotype with higher protein content of both sterol regulatory element binding protein‐1c and acetyl CoA carboxylase. These differences were associated with hepatic steatosis in the LCR including higher liver triglycerides (6.00 ± 0.71 vs. 4.20 ± 0.39 nmol g−1, P= 0.020 value), >2‐fold higher percentage of hepatocytes associated with lipid droplets (54.0 ± 9.2 vs. 22.0 ± 3.5%, P= 0.006), and increased hepatic lipid peroxidation compared to the HCR. Additionally, in rats aged to natural death, LCR livers had significantly greater hepatic injury (fibrosis and apoptosis). We provide novel evidence that selection for low intrinsic aerobic capacity causes reduced hepatic mitochondrial oxidative capacity that increases susceptibility to both hepatic steatosis and liver injury.

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Details

Published: Apr 14, 2009
Vol/Issue: 587(8)
Pages: 1805-1816
License: View

Authors

J

John P. Thyfault

Department of Biomedical Sciences, University of Missouri, Columbia, Missouri; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; Geriatrics, Research, Education and Clinical Center (GRECC), VA Greater Los Angeles Healthcare System, Los Angeles, California; Department of Molecular and...

R

R. Scott Rector

Research Service,Harry S. Truman Memorial Veterans Medical Center,Columbia,Missouri,USA; Department of Nutrition and Exercise Physiology,University of Missouri,Columbia,Missouri,USA; Department of Medicine–Division of Gastroenterology and Hepatology,University of Missouri,Columbia,Missouri,USA

From the Departments of Internal Medicine (J.-a.K., Y.W., J.R.S.), Medical Pharmacology, and Physiology (J.R.S.) and Diabetes and Cardiovascular Center (J.-a.K., Y.W., J.R.S.), University of Missouri–Columbia School of Medicine; and the Harry S. Truman Veterans Affairs Medical Center (J.-a.K., Y.W., J.R.S.), Columbia, Mo.

Research Service,Harry S. Truman Memorial Veterans Medical Center,Columbia,Missouri,USA; Department of Nutrition and Exercise Physiology,University of Missouri,Columbia,Missouri,USA; Department of Medicine–Division of Gastroenterology and Hepatology,University of Missouri,Columbia,Missouri,USA

Cite This Article

John P. Thyfault, R. Scott Rector, Grace M. Uptergrove, et al. (2009). Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury. The Journal of Physiology, 587(8), 1805-1816. https://doi.org/10.1113/jphysiol.2009.169060

Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury

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