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 between different sources. However, there is a paucity of comparative studies regarding the effects and mechanisms of marine and plant ω−3 PUFA on obesity. OBJECTIVE: The aim of this study was to evaluate the effects of fish oil (FO) and perilla oil (PO) on glucolipid metabolism, inflammation, and adipokine in mice fed a high-fat (HF) diet in association with the contribution of toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) pathway. METHODS: C57BL/6J mice and MyD88−/− mice were randomly divided into 4 groups: normal chow diet, HF diet, HF diet accompanied by daily gavage with either FO or PO. After 4 weeks, blood biochemistries, adipocyte histology, mRNA, and protein expression of MyD88-dependent and -independent pathways of TLR4 signaling in epididymal adipose tissue were measured. RESULTS: In C57BL/6J mice, there were no statistical differences between FO and PO in decreasing body weight, glucose, insulin, triglyceride, total cholesterol, interleukin-6, and increasing adipocyte counts. FO and PO decreased mRNA and protein expression of TLR4, MyD88, tumor necrosis factor receptor-associated factor 6, inhibitor of nuclear factor kappa B kinase beta and nuclear factor-kappa B p65. In MyD88−/− mice, the beneficial effects of FO and PO on HF diet-induced metabolism abnormalities and inflammation were abolished. FO and PO had no impacts on mRNA and protein expression of receptor-interacting protein-1, interferon regulate factor 3, and nuclear factor-kappa B p65. CONCLUSION: FO and PO exhibit similar protective effects on metabolic disorders and inflammation through inhibiting TLR4 signaling in a manner dependent on MyD88. These findings highlight plant ω−3 PUFA as an attractive alternative source of marine ω−3 PUFA and reveal a mechanistic insight for preventive benefits of ω−3 PUFA in obesity and related metabolic diseases.