Janin Henkel, Eugenia Alfine, Juliana Saín, Korinna Jöhrens, Daniela Weber, José Pedro Castro, Jeannette König, Christin Stuhlmann, Madita Vahrenbrink, Wenke Jonas, André Kleinridders, Gerhard Paul Püschel
- 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 ofWhile 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.…
MetadatenAuthor details: | Janin HenkelORCiDGND, Eugenia Alfine, Juliana SaínORCiD, Korinna Jöhrens, Daniela WeberORCiD, José Pedro CastroORCiD, Jeannette KönigORCiDGND, Christin StuhlmannORCiD, Madita Vahrenbrink, Wenke JonasORCiDGND, André KleinriddersORCiDGND, Gerhard Paul PüschelORCiDGND |
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DOI: | https://doi.org/10.3390/nu10091326 |
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ISSN: | 2072-6643 |
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Title of parent work (English): | Nutrients |
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Publisher: | Molecular Diversity Preservation International (MDPI) |
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Place of publishing: | Basel |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/09/18 |
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Publication year: | 2018 |
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Release date: | 2018/11/22 |
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Tag: | NASH; PUFA; cholesterol; inflammation; non-alcoholic fatty liver disease (NAFLD); oxidative stress |
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Volume: | 10 |
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Issue: | 9 |
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First page: | 1 |
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Last Page: | 17 |
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Funding institution: | Universität Potsdam, Publikationsfonds |
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Funding number: | PA 2018_63 |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Peer review: | Referiert |
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Grantor: | Publikationsfonds der Universität Potsdam |
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Publishing method: | Open Access |
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License (German): | CC-BY - Namensnennung 4.0 International |
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External remark: | Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 479 |
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