Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis.

Piguet, Anne Christine; Saran, Uttara; Simillion, Cedric André Marie; Keller, Irene; Terracciano, Luigi; Reeves, Helen L; Dufour, Jean-François (2015). Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis. Journal of hepatology, 62(6), pp. 1296-1303. Elsevier 10.1016/j.jhep.2015.01.017

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BACKGROUND & AIMS Unhealthy lifestyles predispose to non-alcoholic steatohepatitis (NASH), which may further result in the development of hepatocellular carcinoma (HCC). Although NASH patients benefit from physical activity, it is unknown whether regular exercise reduces the risk of developing HCC. Therefore, we studied the effect of regular exercise on the development of HCC in male hepatocyte-specific PTEN-deficient mice (AlbCrePten(flox/flox)), which develop steatohepatitis and HCC spontaneously. METHODS Mice were fed a standardized 10% fat diet and were randomly divided into exercise or sedentary groups. The exercise group ran on a motorized treadmill for 60 minutes/day, 5 days/week during 32 weeks. RESULTS After 32 weeks of regular exercise, 71% of exercised mice developed nodules larger than 15 mm(3) vs 100% of mice in the sedentary group. The mean number of tumors per liver was reduced by exercise, as well as the total tumoral volume per liver. Exercise did not affect steatosis and had no effect on the Non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS). Exercise decreased tumor cell proliferation. Mechanistically, exercise stimulated the phosphorylation of AMPK and its substrate raptor, which decreased the kinase activity of mTOR. CONCLUSIONS These data show a benefit of regular exercise on the development of HCC in an experimental model of NASH and offer a rationale for encouraging predisposed patients to increase their physical activity for the prevention of HCC.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
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

UniBE Contributor:

Piguet, Anne Christine; Saran, Uttara; Simillion, Cedric André Marie; Terracciano, Luigi and Dufour, Jean-François

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0168-8278

Publisher:

Elsevier

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

20 Apr 2015 09:44

Last Modified:

01 Jul 2015 16:47

Publisher DOI:

10.1016/j.jhep.2015.01.017

PubMed ID:

25623824

Uncontrolled Keywords:

AMPK; Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; mTOR

BORIS DOI:

10.7892/boris.67160

URI:

https://boris.unibe.ch/id/eprint/67160

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