Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue
Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue
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DOI：
10.1017/s0029665111000565
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发表时间：
2011-11-01
影响因子：
7
通讯作者：
Roche, Helen M.
中科院分区：
文献类型：
--
作者：
Harford, Karen A.;Reynolds, Clare M.;Roche, Helen M.
高脂饮食诱导的肥胖与慢性低度炎症状态相关，其易导致胰岛素抵抗（IR），随后可导致2型糖尿病。巨噬细胞是一种异质性细胞群，有助于启动先天性免疫反应。最近的研究表明，巨噬细胞是肥胖诱导的IR的关键介质，巨噬细胞向肥胖脂肪组织中进行性浸润。这些脂肪组织巨噬细胞被称为经典活化（M1）巨噬细胞。它们释放细胞因子，如IL-1 β、IL-6和TNF α，产生阻断脂肪细胞胰岛素作用的促炎环境，促进IR和2型糖尿病的发展。在瘦个体中，巨噬细胞处于交替激活（M2）状态。M2巨噬细胞参与伤口愈合和免疫调节。伤口愈合巨噬细胞在组织修复和体内平衡中起主要作用，而免疫调节巨噬细胞产生IL-10，一种抗炎细胞因子，可以防止炎症。最近在脂肪组织中已经表征了T细胞积累的功能作用。细胞毒性T细胞是效应T细胞，并且与巨噬细胞分化、活化和迁移有关。细胞毒性T细胞浸润到肥胖脂肪组织被认为是在巨噬细胞积累之前。T细胞衍生的细胞因子，如干扰素γ促进招聘和激活M1巨噬细胞增强脂肪组织炎症和IR。操纵脂肪组织巨噬细胞/T细胞的活性和积累在体内通过饮食脂肪的修改可以减弱脂肪组织炎症，代表一个治疗目标，改善肥胖诱导的IR。
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-1 beta, IL-6 and TNF alpha 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 gamma 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.