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

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...

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Autores principales: Henkel, Janin, Buchheim-Dieckow, Katja, Castro, José P., Laeger, Thomas, Wardelmann, Kristina, Kleinridders, André, Jöhrens, Korinna, Püschel, Gerhard P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893460/
https://www.ncbi.nlm.nih.gov/pubmed/31717358
http://dx.doi.org/10.3390/nu11112709
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author Henkel, Janin
Buchheim-Dieckow, Katja
Castro, José P.
Laeger, Thomas
Wardelmann, Kristina
Kleinridders, André
Jöhrens, Korinna
Püschel, Gerhard P.
author_facet Henkel, Janin
Buchheim-Dieckow, Katja
Castro, José P.
Laeger, Thomas
Wardelmann, Kristina
Kleinridders, André
Jöhrens, Korinna
Püschel, Gerhard P.
author_sort Henkel, Janin
collection PubMed
description 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.
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spelling pubmed-68934602019-12-23 Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH Henkel, Janin Buchheim-Dieckow, Katja Castro, José P. Laeger, Thomas Wardelmann, Kristina Kleinridders, André Jöhrens, Korinna Püschel, Gerhard P. Nutrients Article 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. MDPI 2019-11-08 /pmc/articles/PMC6893460/ /pubmed/31717358 http://dx.doi.org/10.3390/nu11112709 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Henkel, Janin
Buchheim-Dieckow, Katja
Castro, José P.
Laeger, Thomas
Wardelmann, Kristina
Kleinridders, André
Jöhrens, Korinna
Püschel, Gerhard P.
Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
title Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
title_full Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
title_fullStr Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
title_full_unstemmed Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
title_short Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
title_sort reduced oxidative stress and enhanced fgf21 formation in livers of endurance-exercised rats with diet-induced nash
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893460/
https://www.ncbi.nlm.nih.gov/pubmed/31717358
http://dx.doi.org/10.3390/nu11112709
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