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Cited by 104Liver Disease Diagnosis and TreatmentExercise and Physiological ResponsesLiver physiology and pathology

Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

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Fealy, Ciaran E., Haus, Jacob M., Solomon, Thomas P. J., Pagadala, Mangesh, Flask, Chris A., McCullough, Arthur J., Kirwan, John P.·2012·Journal of Applied Physiology
DOI 10.1152/japplphysiol.00127.2012PMC PMC3404833
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Abstract

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis-plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m(2), >5% intrahepatic lipid (IHL) assessed by (1)H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (Vo(2max)) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = -0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.

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  1. [3]3. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 346: 1221–1231, 2002 [DOI] [PubMed] [Google Scholar]
  2. [30]30. Matsuda M, DeFronzo R. Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 22: 1462–1470, 1999 [DOI] [PubMed] [Google Scholar]

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Authors
Fealy, C. E., Haus, J. M., Solomon, T. P. J., Pagadala, M., Flask, C. A., McCullough, A. J., & Kirwan, J. P.
Affiliations
  • Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland;
  • Cleveland Clinic (US)
  • Case Western Reserve University (US)
Corresponding author
Kirwan, John P.
ORCID
Venue
Journal of Applied Physiology
Publisher
American Physiological Society
Published
2012-07-01
Volume
113
Issue
1
Pages
1-6
ISSN
  • 0161-7567 (ISSN-L)
  • 8750-7587
  • 1522-1601
DOI
10.1152/japplphysiol.00127.2012
PMC
PMC3404833
OpenAlex
W2121598176
Cited by
102
References
51
Citations by year
2026: 2 · 2025: 2 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 11 · 2013: 10 · 2012: 2
FWCI
8.38
Type
journal article
Language
en
Open access
Locations
  • Journal of Applied Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR000439)
  • National Institute on Aging (R01AG012834, R01AG12834)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32-DK-0661917)
  • National Center for Research Resources (UL1RR024989)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
non-alcoholic fatty liver disease, hepatocyte apoptosis, short-term exercise, treadmill walking, cytokeratin-18 fragments, alanine aminotransferase, soluble Fas ligand, soluble Fas, fat oxidation, obesity, insulin sensitivity, intrahepatic lipid, nonalcoholic steatohepatitis, exercise training intervention, Matsuda index
MeSH terms
Alanine Transaminase, Aspartate Aminotransferases, Fats, Fatty Liver, Female, Glucose Tolerance Test, Heart Rate, Humans, Insulin Resistance, Male, Middle Aged, Oxygen Consumption, Biomarkers, Walking, Apoptosis, fas Receptor, Hepatocytes, Exercise Movement Techniques, Keratin-18, Non-alcoholic Fatty Liver Disease

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