Delta-6 desaturase conversion of ALA into EPA/DHA has comparable effects on adipocyte size as the direct consumption of EPA/DHA in a model of diet-induced obesity

Omega-3 polyunsaturated fatty acids (n3-PUFA) have numerous reported benefits for cardiometabolic health. A significant limitation of past n3-PUFA research is the inability to conclusively distinguish the effects of different n-3 PUFAs due to the continuous conversion of alpha-linolenic acid (ALA) into eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid through delta-6-desaturase (D6D). We previously reported D6D knockout (KO) mice fed an ALA-rich low-fat diet had lower epididymal white adipose tissue (eWAT, which is a visceral fat depot) weights and smaller adipocytes compared to wildtype (WT) animals due to alterations in triacylglycerol/fatty acid handling. However, it remains unclear how ALA and EPA/DHA independently alter adipocyte size in eWAT in the context of diet-induced obesity. The objective of this study was to investigate how dietary ALA (Flaxseed oil) and EPA/DHA (Menhaden oil) impact eWAT adipocyte size and inflammatory status in high-fat fed D6D-WT and KO mice. Epididymal WAT gene expression and fatty acid composition were measured using real-time quantitative polymerase chain reaction and gas chromatography, respectively. D6D-KO mice fed ALA had no EPA or DHA in eWAT, as expected. Both the endogenous synthesis of EPA/DHA from dietary ALA and the direct consumption of EPA/DHA significantly reduced eWAT weight and adipocyte size in the absence of changes in weight gain or feed efficiency. These reductions were mitigated in ALA-fed D6D-KO mice. In contrast, EPA/DHA supplemented mice showed a significant (p < 0.05) reduction in Tnfa, increase in Ppary and Adipoq with no changes in NfKb, p38, Ccl2, Ccl5, Tlr4 and Nlrp3 gene expression in eWAT compared to ALA-supplemented mice, regardless of D6D genotype. We demonstrate that the consumption of ALA has comparable effects to EPA/DHA on obese eWAT size only when its conversion into EPA/DHA is possible.