EPA/DHA but Not ALA Reduces Visceral Adiposity and Adipocyte Size in High Fat Diet‐Induced Obese Delta‐6 Desaturase Knockout Mice

The objective of this omega-3 feeding study was to elucidate the independent effects of α-linolenic acid (ALA) versus eicosapentaenoic (EPA)/docosahexaenoic acid (DHA) on visceral adiposity and inflammatory signaling in diet-induced obese delta-6 desaturase (Fads2) knockout (KO) mice. Male wildtype (WT) and Fads2 KO mice were fed a high-fat diet (45% kcal from fat) containing either lard (no omega-3s), flaxseed (ALA), or menhaden (EPA/DHA) for 21 weeks. Epididymal white adipose tissue (eWAT) was analyzed for changes in tissue weight, adipocyte size, triacylglycerol (TAG) and fatty acid content, and inflammatory markers. Despite no differences in final body weight, menhaden-fed mice had lower eWAT weight, smaller adipocytes, and lower TAG content compared to lard-fed mice regardless of Fads2 genotype. The eWAT of flaxseed-fed WT mice resembled menhaden-fed mice, while the eWAT of flaxseed-fed KO mice resembled lard-fed mice. No differences were observed in the expression of genes regulating eWAT inflammatory signaling (Tnfα, Nfκb, Mapk14, Mcp1, Ccl5, Tlr4, Nlrp3, or Adipoq) or the abundance of select proteins (p38-MAPK or MCP-1). In conclusion, a high-fat diet containing EPA/DHA, but not ALA, attenuates adipocyte hypertrophy and lowers TAG content but has no effect on eWAT inflammation in a mouse model of long-term diet-induced obesity.