Impact of dietary fatty acids on gene expression of liver-specific knockout of cytochrome P450 reductase

In the present study, we explored the hypothesis that the fatty liver phenotype and associated gene expression changes associated with the specific deletion of the POR gene in adult mouse liver could be abrogated by supplementation of the mouse diet with the very long chain highly unsaturated fatty acids, arachidonic acid (C20:46), eicosapentaenoic acid (C20:53) and docosahexaenoic acid (C22:63). We expected the fatty liver phenotype would not be reduced by the polyunsaturated fatty acids linoleic (C18:26) or linolenic acid (C18:33), since these accumulated in the fatty livers of LivPORKO animals. This proved to be the case. However, we also made two surprising observations. First, control animals fed a diet enriched in PUFA had fatty livers and gene expression profiles similar to animals fed a lard diet, which was deficient in both PUFA and HUFA. Second, while a diet enriched in HUFA did result in reduced steatosis in livers of the LivPOKO animals, fat accumulation was still elevated relative to controls. Array analyses indicated most differences in gene expression were related to fatty acid metabolism and could explain differences in fat accumulation in LivPORKO livers with dietary treatment.

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