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

Nutr Diabetes. 2021 Jun 17;11(1):23. doi: 10.1038/s41387-021-00159-y.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipokines / metabolism
  • Adipose Tissue / metabolism
  • Animals
  • Body Weight / drug effects
  • Diet, High-Fat / methods
  • Fatty Acids, Omega-3 / metabolism
  • Fish Oils / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / metabolism*
  • Obesity / drug therapy
  • Obesity / metabolism*
  • Plant Oils / pharmacology
  • Toll-Like Receptor 4 / metabolism
  • alpha-Linolenic Acid / pharmacology*

Substances

  • Adipokines
  • Fatty Acids, Omega-3
  • Fish Oils
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Plant Oils
  • Toll-Like Receptor 4
  • alpha-Linolenic Acid
  • perilla seed oil