Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue.

Abstract

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

• Authors: Karen A Harford, Clare M Reynolds, Fiona C McGillicuddy, Helen M Roche
• Journal: The Proceedings of the Nutrition Society (Proc Nutr Soc) Vol. 70 Issue 4 Pg. 408-17 (Nov 2011) ISSN: 1475-2719 [Electronic] England
• PMID: 21835098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cytokines
• Dietary Fats

Topics

• Adipose Tissue (immunology)
• Cytokines (metabolism)
• Diet, High-Fat (adverse effects)
• Dietary Fats (adverse effects, immunology)
• Humans
• Inflammation (etiology, immunology)
• Insulin Resistance (immunology)
• Macrophages (metabolism)
• Obesity (complications, immunology)
• T-Lymphocytes (metabolism)