Exercise Attenuates Ribosomal Protein Six Phosphorylation in Fatty Liver Disease
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ORIGINAL ARTICLE
Exercise Attenuates Ribosomal Protein Six Phosphorylation in Fatty Liver Disease Jonathan G. Stine1,2,3,4 · Dandan Xu5 · Kathryn Schmitz2,4,6,7 · Christopher Sciamanna2,4,8 · Scot R. Kimball5 Received: 31 January 2020 / Accepted: 18 March 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Introduction Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH), is a more severe type of NAFLD. Exercise improves NASH, by reversing steatosis, and may arrest fibrosis. However, the mechanisms underlying these interactions are unknown. AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is activated by energy stress. Mammalian target of rapamycin in complex 1 (mTORC1) is a nutrient sensor that regulates protein synthesis. In NASH, AMPK activity is low and mTORC1 is high. In healthy persons, exercise activates AMPK and suppresses mTORC1. We examined the effects of exercise on hepatic ribosomal protein S6 phosphorylation, a downstream target of AMPK and mTORC1 in patients with NASH. Methods Three subjects with biopsy-proven NASH underwent a structured, 20-week aerobic exercise intervention, five-days a week for 30-min at a moderate intensity (40–55% of VO2max). Immunofluorescence staining for rpS6 phosphorylation in hepatic tissue was quantified by ImageJ software. Results Following 20-weeks of aerobic exercise, rpS6 levels were significantly attenuated (3.9 ± 1.9 pre-exercise vs. 1.4 +/0.4 post-exercise, p = 0.04). Conclusions These findings suggest exercise modulates the AMPK/mTORC1 pathway in patients with NASH and may guide the design of future studies into the mechanism of how exercise improves NASH and possibly reverses fibrosis. Keywords Nonalcoholic fatty liver disease · Fatty liver · Physical activity · Fitness · Mechanism Abbreviations AMPK AMP-activated protein kinase mTOR Mammalian target of rapamycin mTORC1 Mammalian target of rapamycin in complex 1 MRI Magnetic resonance imaging NAFLD Nonalcoholic fatty liver disease NASH Nonalcoholic steatohepatitis
NAS NASH Activity Score rpS6 Ribosomal protein S6 VO2max Maximal oxygen consumption
* Jonathan G. Stine [email protected]
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Department of Cellular and Molecular Physiology, The Pennsylvania State University- College of Medicine, Hershey, PA, USA
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Department of Kinesiology, The Pennsylvania State University- College of Medicine, Hershey, PA, USA
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Department of Physical Medicine and Rehabilitation, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey, PA, USA
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Department of Medicine, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey, PA, USA
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Division of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University- Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA Department of Public Health Sciences, The Pennsylvania State University- Milton S. Hershey Medical Cent
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