Alteration of adipose tissue immune cell milieu towards the suppression of inflammation in high fat diet fed mice by flaxseed oil supplementation

Samina Bashir,Farah Khan,Faraz Rashid,Deeba Jairajpuri,Yadhu Sharma,Md Nematullah,Marcia B Aguila

doi:10.1371/journal.pone.0223070

Abstract

The present study evaluates the effect of flaxseed oil (FXO) supplementation on adipose tissue macrophages (ATM’s), E and D series resolvin (Rv) levels and adipose tissue inflammation. Male C57BL/6J mice were divided into five groups (n = 5): lean group (given standard chow diet), HFD group given high fat diet (approx. 18 weeks) till they developed insulin resistance and 4, 8 or 16 mg/kg group (HFD group later orally supplemented with 4, 8 or 16 mg/kg body weight flaxseed oil) for 4 weeks.The present study showed that FXO supplementation led to enhanced DHA, EPA, RvE1-E2, RvD2, RvD5- D6, IL-4, IL-10 and arginase 1 levels in ATMs together with altered immune cell infiltration and reduced NF-κB expression. The FXO supplementation suppresses immune cell infiltration into adipose tissue and alters adipose tissue macrophage phenotype towards the anti-inflammatory state via enhancement of E and D series resolvins, arginase 1 expression and anti-inflammatory cytokines level (IL-4 and IL-10.) leading to amelioration of insulin resistance in flaxseed oil supplemented HFD mice.

Highlights

Obesity is a state of chronic low-grade inflammation that originates due to the altered resolution of inflammation
This leads to a shift in cytokine levels from anti-inflammatory nature to pro-inflammatory that further leads to systemic inflammation and insulin resistance [21]
Serhan and Colleagues identified and characterized novel resolving lipid mediators namely lipoxins, resolvins and protectins families of endogenously produced, lipid-derived substances that were found to play a dynamic role in the resolution of inflammation [22]

Summary

Introduction

Obesity is a state of chronic low-grade inflammation that originates due to the altered resolution of inflammation This inflammatory condition disturbs the balance between the metabolic pathway and immune system leading to obesity-associated conditions such as insulin resistance, type 2 diabetes, atherosclerosis and non-alcoholic fatty liver disease [1].Adipose tissueresident immune cells, especially macrophages are the key contributors to initiate inflammatory cascade in adipose tissue. The altered resolution of inflammation under conditions of obesity and insulin resistance may be modulated by therapeutic interventions or modification in diet/ lifestyle that lead to macrophage switching [4]. On exposure to saturated fatty acids, macrophages in vitro express increased pro-inflammatory genes and cytokines (e.g., TNF-α, IL6, and CXCL1/KC) while supplementation with n-3 fatty acids from dietary sources like fish oil leads to reduced proinflammatory cytokines production and inhibition of M1 states in ATMs [4, 5]. How the balance of lipid mediators changes during the course of obese and insulin resistance is still unclear

Methods

Results

Conclusion