Menhaden oil but not flaxseed oil reduces hepatic lipogenic gene expression independent of delta-6 desaturase activity

Abstract:
The Fads2 gene encodes for the delta-6-desaturase (D6D) enzyme, the rate-limiting step in the production of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from their precursor, alpha-linolenic acid (ALA). We and others have demonstrated the ability of EPA and DHA to modify triacylglycerol storage and alter lipogenic and lipolytic pathways in liver. In contrast, the impact of ALA on these processes is less understood. To address this gap in knowledge, we fed male wildtype (WT) and D6D knockout (KO) mice low-fat diets (7% kcal from fat) containing either lard (no n-3 LCPUFA), flaxseed oil (ALA rich), or menhaden oil (EPA/DHA rich) for 21 weeks and then examined hepatic fatty acid metabolism. Fatty acid composition and markers of lipogenesis, lipolysis, and triglyceride synthesis were analyzed using gas chromatography, colorimetric assay, histological evaluation, and RT-qPCR. Mice fed the menhaden diet had a significant reduction in total hepatic TAG concentration compared to both lard and flax-fed mice as well as alterations in the concentration of key n-3 and n-6 PUFA in both TAG and PL fractions (all P < 0.05), compared to lard and flax-fed mice. Further, mice fed the menhaden diet had significant alterations in the expression of key lipogenic (Scd1, Srebp-1c, Fasn, Fads1, Fads2), glyceroneogenic (Pck1, Aqp9), and triacylglycerol synthesis (Agpat3) genes compared to lard and flax-fed mice. Finally, these effects appear independent of delta-6 desaturase activity, as no relevant differences in gene expression were detected between WT and KO mice fed the same diet despite the expected differences in hepatic fatty acid content. In conclusion, this study demonstrates that the distinct influence of flaxseed and menhaden oils on the regulation of fatty acid metabolism and deposition in murine hepatic tissue is not modified by D6D.