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Nutrients. 2018 Sep 18;10(9). pii: E1326. doi: 10.3390/nu10091326.

Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol.

Author information

1
Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany. jhenkel@uni-potsdam.de.
2
German Institute of Human Nutrition, Junior Research Group Central Regulation of Metabolism; D-14558 Nuthetal, Germany. Eugenia.Alfine@dife.de.
3
German Center for Diabetes Research (DZD), D-85764 München-Neuherberg, Germany. Eugenia.Alfine@dife.de.
4
Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany. jsain@fbcb.unl.edu.ar.
5
Department of Biological Sciences, Food Science and Nutrition, Faculty of Biochemistry and Biological Sciences, National University of the Litoral (UNL), Santa Fe S3000, Argentina. jsain@fbcb.unl.edu.ar.
6
Institute of Pathology, Carl Gustav Carus University Hospital Dresden; D-01307 Dresden, Germany. korinna.joehrens@uniklinikum-dresden.de.
7
Department of Molecular Toxicology, German Institute of Human Nutrition; D-14558 Nuthetal, Germany. Daniela.Weber@dife.de.
8
Department of Molecular Toxicology, German Institute of Human Nutrition; D-14558 Nuthetal, Germany. Jose.Castro@dife.de.
9
Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Jose.Castro@dife.de.
10
Department of Molecular Toxicology, German Institute of Human Nutrition; D-14558 Nuthetal, Germany. Jeannette.Koenig@dife.de.
11
Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany. stuhlman@uni-potsdam.de.
12
Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany. vahrenbrink@uni-potsdam.de.
13
German Center for Diabetes Research (DZD), D-85764 München-Neuherberg, Germany. Wenke.Jonas@dife.de.
14
Department of Experimental Diabetology, German Institute of Human Nutrition; D-14558 Nuthetal, Germany. Wenke.Jonas@dife.de.
15
German Institute of Human Nutrition, Junior Research Group Central Regulation of Metabolism; D-14558 Nuthetal, Germany. Andre.Kleinridders@dife.de.
16
German Center for Diabetes Research (DZD), D-85764 München-Neuherberg, Germany. Andre.Kleinridders@dife.de.
17
Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany. gpuesche@uni-potsdam.de.

Abstract

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.

KEYWORDS:

NASH; PUFA; cholesterol; inflammation; non-alcoholic fatty liver disease (NAFLD); oxidative stress

PMID:
30231595
PMCID:
PMC6164134
DOI:
10.3390/nu10091326
[Indexed for MEDLINE]
Free PMC Article

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