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.

Uso do teste de duplos esforços para avaliação da capacidade aeróbia de ratos obesos induzidos por dieta

“…After four weeks of exposure to this hyperlipidic diet, there was significant increase in body weight of the animals from the obese group and reduction in the insulin sensitivity when compared with the animals from the control group (figures 2 and 3), which only received standard chow as food, highlighting the obesogenic effect of the diet 22 and the correlation between obesity and metabolic alterations caused by fat excess 25 . The cytokines released by the excessive adipose tissue may generate a scenario of peripheral systemic inflammation 26,27 , altering the insulin signaling and initiating a possible insulin resistant status 28 .…”

Examination of myeloperoxidase activity, as an indicator of inflammation in obese participants with metabolic syndrome

“…Gojaznost je povezana sa hroničnim stanjem inflamacije niskog intenziteta, uzrokovanom progresivnom infiltracijom makrofaga u masno tkivo gojaznih osoba. Citokini produkovani od strane makrofaga i adipokini produkovani od strane masnih ćelija posledično uzrokuju inflamaciju [12]. Akumulacija makrofaga u masnom tkivu povećava se sa uvećanjem količine masnog tkiva, što uzrokuje povećanu produkciju proinflamatornih citokina i molekula akutne-faze i doprinosi pojavi patoloških promena kod gojaznih.…”

Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

“…Adipocytes damaged by high lipid intake produce signals that promote a proinflammatory Type 1 immune response. The number of T cells is increased in the enlarged VAT during obesity in response to adipose tissue-specific factors (12). Adipose tissue-associated regulatory T cells (Tregs) protect against (13), while the recruitment of Type 1 CD4 and CD8 + T lymphocytes precedes, metabolic alterations in obesity (14,15).…”