TY  - GEN
A1  - Henkel, Janin
A1  - Buchheim-Dieckow, Katja
A1  - Castro, José Pedro
A1  - Laeger, Thomas
A1  - Wardelmann, Kristina
A1  - Kleinridders, André
A1  - Jöhrens, Korinna
A1  - Püschel, Gerhard Paul
T1  - Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - 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.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 807 
KW  - NAFLD
KW  - NASH
KW  - endurance exercise
KW  - FGF21
KW  - glucose intolerance
KW  - cholesterol
KW  - oxidative stress
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-442384
SN  - 1866-8372
IS  - 807
ER  - 
TY  - JOUR
A1  - Henkel, Janin
A1  - Buchheim-Dieckow, Katja
A1  - Castro, José Pedro
A1  - Laeger, Thomas
A1  - Wardelmann, Kristina
A1  - Kleinridders, André
A1  - Jöhrens, Korinna
A1  - Püschel, Gerhard Paul
T1  - Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
JF  - Nutrients
N2  - 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.
KW  - NAFLD
KW  - NASH
KW  - endurance exercise
KW  - FGF21
KW  - glucose intolerance
KW  - cholesterol
KW  - oxidative stress
Y1  - 2019
U6  - https://doi.org/10.3390/nu11112709
SN  - 2072-6643
VL  - 11
IS  - 11
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Henkel, Janin
A1  - Alfine, Eugenia
A1  - Saín, Juliana
A1  - Jöhrens, Korinna
A1  - Weber, Daniela
A1  - Castro, José Pedro
A1  - König, Jeannette
A1  - Stuhlmann, Christin
A1  - Vahrenbrink, Madita
A1  - Jonas, Wenke
A1  - Kleinridders, André
A1  - Püschel, Gerhard Paul
T1  - Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol
JF  - Nutrients
N2  - While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.
KW  - non-alcoholic fatty liver disease (NAFLD)
KW  - NASH
KW  - cholesterol
KW  - PUFA
KW  - inflammation
KW  - oxidative stress
Y1  - 2018
U6  - https://doi.org/10.3390/nu10091326
SN  - 2072-6643
VL  - 10
IS  - 9
SP  - 1
EP  - 17
PB  - Molecular Diversity Preservation International (MDPI)
CY  - Basel
ER  - 
TY  - GEN
A1  - Henkel, Janin
A1  - Alfine, Eugenia
A1  - Saín, Juliana
A1  - Jöhrens, Korinna
A1  - Weber, Daniela
A1  - Castro, José Pedro
A1  - König, Jeannette
A1  - Stuhlmann, Christin
A1  - Vahrenbrink, Madita
A1  - Jonas, Wenke
A1  - Kleinridders, André
A1  - Püschel, Gerhard Paul
T1  - Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol
T2  - Nutrients
N2  - While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 479 
KW  - non-alcoholic fatty liver disease (NAFLD)
KW  - NASH
KW  - cholesterol
KW  - PUFA
KW  - inflammation
KW  - oxidative stress
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-419773
ER  -