Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil

Immunol Invest. 2015;44(5):451-69. doi: 10.3109/08820139.2015.1025960.

Abstract

The present study was designed to assess the potential of supplementation of diet with Flaxseed (Linum usitatissimum, L.) oil (FXO), on obesity-related inflammation and reversal of obesity-induced insulin resistance. Swiss Albino mice, C57bl/6 mice and co-culture of 3T3-L1 adipocytes - RAW 264.7 macrophages to mimick obese adipose tissue environment were used for the study. Oral gavage of FXO at concentrations of 4, 8 or 16 mg/kg body weight (bwt) for 4 weeks or high-fat diet (HFD, 60% energy as fat) supplemented with dietary FXO (4, 8 or 16 mg/kg bwt) was given to the mice. FXO was characterised using gas chromatography - mass spectrometry. FXO supplemented HFD-fed mice (4 mg/kg bwt exhibited reduced adiposity index, serum glucose levels and triglycerides (8 and 16 mg/kg bwt) and improvement in insulin sensitisation (4, 8 and 16 mg/kg bwt) when compared with HFD mice. The co-culture showed a dose-dependent shift in cytokines towards anti-inflammatory (IL-4) state, with a decrease in pro-inflammatory TNF-α (p < 0.05). For immunomodulatory studies a dose-dependent increase (p < 0.05) was observed in antigen-specific levels of Th2 (IL-4) cytokine, serum anti-ova IgG1 and IgE levels. Suppression in anti-ova IgG2a, IgG2b, and IgG3 and antigen-specific Th1 cytokines like TNF-α and IFN-γ significantly (p < 0.05) was observed at 16 mg/kg bwt dosage. The results indicate that FXO exhibits an anti-inflammatory immunomodulatory potential and may partially relieve symptoms of obesity-associated insulin resistance.

Keywords: Anti-inflammatory; cell-mediated immune response; co-culture; humoral immune response; immunomodulation; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adiposity / drug effects
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Coculture Techniques
  • Cytokines / metabolism
  • Diet, High-Fat
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Immunologic
  • Drug Evaluation, Preclinical
  • Glucose Tolerance Test
  • Hypersensitivity, Delayed / etiology
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / prevention & control
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Insulin Resistance*
  • Linseed Oil / administration & dosage
  • Linseed Oil / pharmacology
  • Linseed Oil / therapeutic use*
  • Lipids / blood
  • Liver / drug effects
  • Liver / pathology
  • Lymphocyte Activation / drug effects
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / physiopathology*
  • Ovalbumin / immunology
  • Phytotherapy
  • RAW 264.7 Cells
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Immunoglobulin G
  • Immunologic Factors
  • Lipids
  • Immunoglobulin E
  • Linseed Oil
  • Ovalbumin