Dataset Information

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

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 ?6-poly-unsaturated fatty acids (?6-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 ?6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.

SUBMITTER: Henkel J

PROVIDER: S-EPMC6164134 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Henkel Janin J Alfine Eugenia E Saín Juliana J Jöhrens Korinna K Weber Daniela D Castro José P JP König Jeannette J Stuhlmann Christin C Vahrenbrink Madita M Jonas Wenke W Kleinridders André A Püschel Gerhard P GP

Nutrients 20180918 9

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 ca ...[more]

PMID: 30231595

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Project description:The epigenetic landscape is vulnerable to variations in diet. Here, we investigated the influence of different PUFA dietary supplements on rodents’ nervous system development and functions and potential consequences for neurodegenerative disorders. We have previously studied the genomic plasticity of these biofunctions in mice fed on high n-3 PUFA enriched diet (ERD). In conjunction, in the present study, we introduced a second equicaloric diet with n-3 PUFA optimally balanced by n-6 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline. Randomly grouped C57BL/6j mice were fed on any of these three diets from their neonatal age to late adolescent. Post-euthanasia, the transcriptomic landscape of hemibrains was investigated in parallel for two epigenetic mechanisms, namely the miRNA profile and DNA methylation. Integrating data we focused on those genes which had both hypermethylated CpG islands and silenced transcripts. Of these, 308 and 131 genes were perturbed by ERD and BLD, respectively, in comparison to the baseline. Also, miRNA:mRNA pairs were screened to identify those overexpressed miRNAs that silenced gene transcription. There were 18 and 39 miRNAs that met the cutoff in ERD- and BLD-fed mice, respectively. The majority of miRNAs overexpressed by BLD are associated with Alzheimer’s and schizophrenia. BLD allowed hypermethylation of those genes that enriched the networks associated with calcium-releasing neurotransmitters. Downstream networks leading to LTP, memory, cognition and learning were perturbed in sync. ERD permitted hypermethylation of genes that enrich the cytoskeletal development network and promote the formation of neuronal precursors. We present the conclusions taking into full account the limited knowledge regarding the epigenetic influence on biofunctions. Since this study has single time point, we could not verify if these functional attributes are the cause or the consequences of epigenetic plasticity. Hence, a more comprehensive study in this regard is essential.

Dataset Information

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

Publications

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

Similar Datasets

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