Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies.
Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies.
复制标题
DOI：
10.3389/fendo.2013.00052
复制
发表时间：
2013
影响因子：
5.2
通讯作者：
Roche HM
中科院分区：
文献类型：
--
作者：
McArdle MA;Finucane OM;Connaughton RM;McMorrow AM;Roche HM
肥胖和相关的慢性炎症引发胰岛素抵抗（IR）状态。化学引诱剂如MCP-1和MIF以及细胞因子IL-6、TNF-α和IL-1β的分泌，吸引免疫细胞包括树突状细胞、T细胞和巨噬细胞进入脂肪组织（AT）。功能失调的AT脂质代谢导致循环游离脂肪酸增加，在浸润细胞群中启动炎症信号级联反应。促炎细胞因子的反馈循环加剧了这种病理状态，进一步推动免疫细胞浸润和细胞因子分泌，破坏胰岛素信号级联。正常AT功能的破坏可导致肝脏和骨骼肌葡萄糖稳态的缺陷，导致全身IR，最终发展为2型糖尿病。针对炎症环境的药物策略可能具有一定的潜力；然而，围绕这种药物方法存在许多安全问题。营养抗炎干预可以提供更合适的长期替代方案；虽然它们可能不如一些药物抗炎剂有效，但这对于长期治疗可能是有利的。这篇综述将探讨肥胖AT的生物学、炎症的开始和胰岛素抵抗环境；以及饮食抗炎成分/功能性营养素可能有益的机制。
Obesity and associated chronic inflammation initiate a state of insulin resistance (IR). The secretion of chemoattractants such as MCP-1 and MIF and of cytokines IL-6, TNF-α, and IL-1β, draw immune cells including dendritic cells, T cells, and macrophages into adipose tissue (AT). Dysfunctional AT lipid metabolism leads to increased circulating free fatty acids, initiating inflammatory signaling cascades in the population of infiltrating cells. A feedback loop of pro-inflammatory cytokines exacerbates this pathological state, driving further immune cell infiltration and cytokine secretion and disrupts the insulin signaling cascade. Disruption of normal AT function is causative of defects in hepatic and skeletal muscle glucose homeostasis, resulting in systemic IR and ultimately the development of type 2 diabetes. Pharmaceutical strategies that target the inflammatory milieu may have some potential; however there are a number of safety concerns surrounding such pharmaceutical approaches. Nutritional anti-inflammatory interventions could offer a more suitable long-term alternative; whilst they may be less potent than some pharmaceutical anti-inflammatory agents, this may be advantageous for long-term therapy. This review will investigate obese AT biology, initiation of the inflammatory, and insulin resistant environment; and the mechanisms through which dietary anti-inflammatory components/functional nutrients may be beneficial.