title: 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.affiliation: Nutrigenomics Research Group, UCD Conway Institute, Belfield, University College Dublin, Republic of Ireland.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Harford
authors.forename: Clare M
authors.initials: CM
authors.lastname: Reynolds
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McGillicuddy
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D007333:Insulin Resistance / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004041:Dietary Fats