Exercise Attenuates the Transition from Fatty Liver to Steatohepatitis and Reduces Tumor Formation in Mice.

Guarino, Maria; Kumar, Pavitra; Felser, Andrea; Terracciano, Luigi M; Guixé-Muntet, Sergi; Humar, Bostjan; Foti, Michelangelo; Nuoffer, Jean-Marc; St-Pierre, Marie V.; Dufour, Jean-François (2020). Exercise Attenuates the Transition from Fatty Liver to Steatohepatitis and Reduces Tumor Formation in Mice. Cancers, 12(6) MDPI AG 10.3390/cancers12061407

[img]
Preview
Text
cancers-12-01407-v2 (1).pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (9MB) | Preview

Non-alcoholic fatty liver disease (NAFLD) leads to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. For sedentary patients, lifestyle interventions combining exercise and dietary changes are a cornerstone of treatment. However, the benefit of exercise alone when dietary changes have failed is uncertain. We query whether exercise alone arrests the progression of NASH and tumorigenesis in a choline-deficient, high-fat diet (CD-HFD) murine model. Male C57Bl/6N mice received a control diet or CD-HFD for 12 weeks. CD-HFD mice were randomized further for 8 weeks of sedentariness (SED) or treadmill exercise (EXE). CD-HFD for 12 weeks produced NAFL. After 20 weeks, SED mice developed NASH and hepatic adenomas. Exercise attenuated the progression to NASH. EXE livers showed lower triglycerides and tumor necrosis factor-α expression, less fibrosis, less ballooning, and a lower NAFLD activity score than did SED livers. Plasma transaminases and triglycerides were lower. Exercise activated AMP-activated protein kinase (AMPK) with inhibition of mTORC1 and decreased S6 phosphorylation, reducing hepatocellular adenoma. Exercise activated autophagy with increased LC3-II/LC3-I and mitochondrial recruitment of phosphorylated PTEN-induced kinase. Therefore, exercise attenuates the transition from NAFL to NASH, improves biochemical and histological parameters of NAFLD, and impedes the progression of fibrosis and tumorigenesis associated with enhanced activation of AMPK signaling and favors liver autophagy. Our work supports the benefits of exercise independently of dietary changes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Guarino, Maria; Kumar, Pavitra; Felser, Andrea Debora; Guixé Muntet, Sergi; Nuoffer, Jean-Marc; St-Pierre, Marie and Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2072-6694

Publisher:

MDPI AG

Language:

English

Submitter:

Karin Balmer

Date Deposited:

09 Nov 2020 14:48

Last Modified:

09 Nov 2020 14:48

Publisher DOI:

10.3390/cancers12061407

PubMed ID:

32486073

Uncontrolled Keywords:

ER stress exercise high-fat diet non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatocellular carcinoma (HCC), liver fibrosis

BORIS DOI:

10.7892/boris.147773

URI:

https://boris.unibe.ch/id/eprint/147773

Actions (login required)

Edit item Edit item
Provide Feedback