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

Lookup NU author(s): Dr Cedric Simillion, Professor Helen ReevesORCiD


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Background & Aims: Unhealthy lifestyles predispose people 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 min/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 nonalcoholic 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 beneficial effect 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. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Piguet AC, Saran U, Simillion C, Keller I, Terracciano L, Reeves HL, Dufour JF

Publication type: Article

Publication status: Published

Journal: Journal of Hepatology

Year: 2015

Volume: 62

Issue: 6

Pages: 1296-1303

Print publication date: 01/06/2015

Online publication date: 23/01/2015

Acceptance date: 14/01/2015

ISSN (print): 0168-8278

ISSN (electronic): 1600-0641

Publisher: Elsevier BV


DOI: 10.1016/j.jhep.2015.01.017


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Funder referenceFunder name
141798Swiss Science Foundation (Sinergia)
Health-F2-2009-241762''Fatty Liver Inhibition of Progression'' (FLIP) project - European Union Seventh Framework Programme (FP7)
KFS 2541-02-2010Oncosuisse