TY - JOUR
T1 - Exercise Attenuates Ribosomal Protein Six Phosphorylation in Fatty Liver Disease
AU - Stine, Jonathan G.
AU - Xu, Dandan
AU - Schmitz, Kathryn
AU - Sciamanna, Christopher
AU - Kimball, Scot R.
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s10620-020-06226-1
DO - 10.1007/s10620-020-06226-1
M3 - Article
C2 - 32239376
AN - SCOPUS:85083246920
SN - 0163-2116
VL - 65
SP - 3238
EP - 3243
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 11
ER -