Department of Biochemistry and Molecular Genetics, Hospital Clínic, Centre Esther Koplowitz, IDIBAPS, CIBERehd, and Department of Physiological Sciences I, University of Barcelona, Barcelona, Spain.
Curr Opin Clin Nutr Metab Care. 2011 Jul;14(4):347-53. doi: 10.1097/MCO.0b013e32834777fa.
Obesity is a major risk factor for metabolic syndrome-related comorbidities such as insulin resistance, type-II diabetes, and nonalcoholic fatty liver disease (NAFLD). A wealth of evidence indicates that the associated pathologies of the metabolic syndrome are aggravated by the presence of a chronic state of 'low-grade' inflammation in the adipose tissue. This article discusses recent data implicating lipoxygenases and especially 5-lipoxygenase and its derived products, the leukotrienes, in mounting adipose tissue inflammation and related pathologies in obesity.
Overexpression of selected members of the 5-lipoxygenase pathway and increased leukotriene production are common findings in excessive visceral fat depots. In these conditions, 5-lipoxygenase products exert potent proinflammatory actions including induction of nuclear factor-κB and secretion of proinflammatory and insulin resistant adipokines (i.e., monocyte chemotactic protein-1, tumor necrosis factor-α, macrophage inflammatory protein-1γ, and interleukin-6) by adipose tissue. The 5-lipoxygenase pathway also plays a major role in mounting inflammation in hepatic tissue and has emerged as a pathogenic factor in obesity-induced NAFLD. Similar role in NAFLD has been proposed for the 12/15-lipoxygenase pathway.
Modulation of lipoxygenases represents a novel target in the prevention of adipose tissue and hepatic dysfunction related to the metabolic syndrome.
肥胖是代谢综合征相关合并症的一个主要危险因素，如胰岛素抵抗、二型糖尿病和非酒精性脂肪肝（NAFLD）。大量证据表明，代谢综合征的相关病理是由脂肪组织中慢性“低度”炎症状态加剧的。本文讨论了最近的数据，这些数据表明脂氧合酶，特别是 5-脂氧合酶及其衍生产物白三烯，在肥胖症中引发脂肪组织炎症和相关病理。
在过多的内脏脂肪组织中，5-脂氧合酶途径的某些成员的过度表达和白三烯产生的增加是常见的发现。在这些情况下，5-脂氧合酶产物通过脂肪组织发挥强烈的促炎作用，包括诱导核因子-κB 和分泌促炎和胰岛素抵抗的脂肪因子（即单核细胞趋化蛋白-1、肿瘤坏死因子-α、巨噬细胞炎性蛋白-1γ 和白细胞介素-6）。5-脂氧合酶途径在肝脏组织中引发炎症方面也起着主要作用，并已成为肥胖诱导的 NAFLD 的致病因素。12/15-脂氧合酶途径在 NAFLD 中也具有类似的作用。
脂氧合酶的调节代表了预防与代谢综合征相关的脂肪组织和肝功能障碍的一个新靶点。
