Dietary EPA and DHA prevent changes in white adipose tissue omega-3 PUFA and oxylipin content associated with a Fads2 deficiency

Abstract

Fatty acid desaturase 2 (Fads2) encodes the delta-6 desaturase (D6D) enzyme, which is rate-limiting for the endogenous production of omega-3 long-chain polyunsaturated fatty acids (LC-PUFA). Numerous studies have reported the cardiometabolic health benefits of omega-3 LC-PUFA. Humans carrying genetic variants in the FADS2 gene have reduced levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as oxylipins, in blood, erythrocytes and white adipose tissue (WAT). Similar findings have been reported in whole-body Fads2−/− mice fed a diet deficient in omega-3 LC-PUFA. The objective of this study was to determine if a diet containing EPA and DHA would prevent the deficiencies in WAT lipid profiles seen in Fads2−/− mice fed a diet containing only ALA. Male C57BL/6 J Fads2−/− and wild type (WT) mice were fed a low fat (7% w/w) diet for 9 weeks containing either flaxseed oil + ARASCO (FD, containing~53% ALA) or menhaden oil (MD, containing~14% EPA and 10% DHA). Fads2−/− mice fed an ALA-enriched diet had reduced body weight, little-to-no omega-3 LC-PUFA and a near complete loss of all omega-3 derived oxylipins in both epididymal and inguinal WAT (P<.05) compared to their WT counterparts, as well as altered expression of key regulators of the fatty acid desaturase pathway. However, Fads2−/− mice fed a diet containing EPA and DHA prevented most of these changes. This study provides evidence that a diet containing EPA and DHA provides a nutritional strategy to prevent alterations in WAT lipid content caused by reduced D6D activity.