Effects of Dietary Fatty Acids on Hepatic Function and Gene Expression in a Model of Hepatic Steatosis

Abstract

NADPH‐cytochrome P450 reductase (POR) is required for the function of many microsomal enzymes, including cytochrome P450 monooxygenases In liver, the P450 enzymes play major roles in the metabolism and detoxification of nutrients, pharmaceuticals and toxic compounds. Deletion of the POR gene in mice (liver‐POR‐null), results in reduced serum cholesterol and triglyceride levels and sizable accumulation of triglycerides resulting in steatosis, which may result in inflammation and fibrosis. In previous work, we reported liver‐POR‐null animals have reduced expression of genes involved in elongation and desaturation of PUFA (polyunsaturated fatty acid), which leads to a reduced capacity to synthesize HUFA (highly unsaturated fatty acid). In the present studies, we have examined the fates and regulatory effects of feeding mice diets that are enriched in saturated fat from lard (16:0 and 18:0), PUFA from canola oil (18:2 and 18:3), and HUFA from a fish and fungal oil mixture (20:4, 20:5 and 22:5). The results point to very profound and unique differences in the storage capacity for these fats in adipose tissue, metabolic fates in liver, and effects on gene expression in liver. The deletion of POR exacerbates the problems associated with dietary fat and leads to additional gene expression changes that favor steatosis and inflammation. This work was supported by a grant from the Charitable Leadership Foundation.