Flax oil and fish oil-enriched diets differentially impact lipid metabolism and tissue oxylipin distributions in the Syrian hamster

Abstract: The Western food supply has become omega-6 (n6) PUFAs rich, with the ratio to omega-3 (n3) PUFAs reaching ~20:1 which may enhance a proinflammatory/vasoconstrictive state. Increasing n3 intake may improve dietary healthfulness, but effects may differ with the specific n3 fatty acid consumed. To explore the impact of dietary n3 type on lipid metabolism, hamsters were fed 40% caloric fat diets with 1:1:1 SFA/MUFA/PUFA levels with PUFA n6:n3 ratios of either 20:1 or 3:1, created using blends of corn oil (CornO), alpha-linoleic acid (ALA)-rich flax oil (FlaxO) and/or eicosapentaenoic/docosahexaenoic acid (EPA/DHA)-rich fish oil (FishO) on a background of ~30% butter fat and ~20% olive oil. Animals maintained on a CornO-based 20:1 n6/n3 diet for 8 weeks were either maintained on CornO or switched to isocaloric 3:1 n6/n3 FlaxO- or FishO-enriched diets for 6wk. Hepatic lipid metabolism gene expression, plasma fatty acid and oxylipin profiles, and liver and adipose oxylipin levels in complex lipid pools were measured. Relative to the CornO diet, FishO reduced liver delta-5 and delta-6 desaturase expression, while FlaxO reduced fatty acid elongase ELOVL5 expression. Plasma fatty acids and oxylipins reflected the dietary fat sources and time on diet. In the liver, FishO enriched phospholipid and triglyceride EPA-derived oxylipins 7- to 5-fold, while FlaxO enriched cholesteryl ester and triglycerides ALA-derived epoxides ~4-fold. In adipose tissue, both FishO and FlaxO reduced adipose triglyceride linoleate-derived oxylipins 2-fold, while ALA-epoxides were ~2.5-fold higher with FlaxO, and the EPA-derived epoxides and alcohols were 3-6fold higher with FishO. Therefore, both FishO and FlaxO suppressed liver long chain fatty acid synthesis, while having distinct impacts on bioactive lipids in tissue lipid sub-compartments, beyond shifts related to the n3 source. Together, these findings suggest that considering the n6/n3 ratio alone is overly simplistic, and that the balance of n3 sources in diets should be considered.