MyD88 determines the protective effects of fish oil and perilla oil against metabolic disorders and inflammation in adipose tissue from mice fed a high-fat diet

Background: The beneficial effects of ω-3 polyunsaturated fatty acids (PUFA) vary by source, yet few studies directly compare marine and plant ω-3 PUFA on obesity. Objective: Evaluate effects of fish oil (FO; EPA/DHA) and perilla oil (PO; ALA) on glucolipid metabolism, inflammation, and adipokines in high-fat (HF) diet-fed mice, focusing on TLR4/MyD88 pathway involvement. Methods: Male C57BL/6J and MyD88−/− mice were randomized to normal chow (NC), HF, HF+FO (0.5 g/kg/day), or HF+PO (0.5 g/kg/day) for 4 weeks (n=10/group for C57BL/6J; n=6/group for MyD88−/−). Serum biochemistry, adipose histology, and epididymal adipose TLR4 pathway gene/protein expression (MyD88-dependent and -independent) were assessed. Results: In C57BL/6J mice, FO and PO similarly reduced body weight gain, glucose, insulin, TG, TC, IL-6, and adipocyte hypertrophy versus HF, with no significant differences between FO and PO for most outcomes (HDL-C and LDL-C were higher in PO than FO). FO and PO lowered adipose TLR4, MyD88, TRAF6, IKKβ, and NF-κB p65 expression. In MyD88−/− mice, the metabolic and anti-inflammatory benefits of FO/PO were abolished; FO/PO did not affect RIP1, IRF3, or NF-κB p65, though TLR4 mRNA decreased. Conclusion: FO and PO confer similar protection against HF diet-induced metabolic disorders and adipose inflammation by inhibiting TLR4 signaling in a MyD88-dependent manner, supporting plant ω-3 PUFA as an alternative to marine ω-3 PUFA for prevention of obesity-related metabolic disease.

Feng Wang, Mingyuan Hu, Hangju Zhu, Chao Yang, Hui Xia, Xian Yang, Ligang Yang, Guiju Sun