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Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH

1
Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany
2
Department of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
3
Department of Molecular Toxicology, German Institute of Human Nutrition, D-14558 Nuthetal, Germany
4
Department of Experimental Diabetology, German Institute of Human Nutrition, D-14558 Nuthetal, Germany
5
German Center for Diabetes Research (DZD), D-85764 München-Neuherberg, Germany
6
Junior Research Group Central Regulation of Metabolism, German Institute of Human Nutrition, D-14558 Nuthetal, Germany
7
Institute of Pathology, Carl Gustav Carus University Hospital Dresden, D-01307 Dresden, Germany
*
Author to whom correspondence should be addressed.
Equally contributing first authors.
Nutrients 2019, 11(11), 2709; https://doi.org/10.3390/nu11112709
Received: 30 September 2019 / Revised: 31 October 2019 / Accepted: 5 November 2019 / Published: 8 November 2019
(This article belongs to the Special Issue Nutrition and Exercise Metabolism)
Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production. View Full-Text
Keywords: NAFLD; NASH; endurance exercise; FGF21; glucose intolerance; cholesterol; oxidative stress NAFLD; NASH; endurance exercise; FGF21; glucose intolerance; cholesterol; oxidative stress
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Henkel, J.; Buchheim-Dieckow, K.; Castro, J.P.; Laeger, T.; Wardelmann, K.; Kleinridders, A.; Jöhrens, K.; Püschel, G.P. Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH. Nutrients 2019, 11, 2709.

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