摘要
Expansion of adipose tissue mass, the distinctive feature of obesity, is associated with low-grade inflammation. White adipose tissue secretes a diverse range of adipokines, a number of which are inflammatory mediators (such as TNFα, IL-1β, IL-6, monocyte chemoattractant protein 1). The production of inflammatory adipokines is increased with obesity and these adipokines have been implicated in the development of insulin resistance and the metabolic syndrome. However, the basis for the link between increased adiposity and inflammation is unclear. It has been proposed previously that hypoxia may occur in areas within adipose tissue in obesity as a result of adipocyte hypertrophy compromising effective O2 supply from the vasculature, thereby instigating an inflammatory response through recruitment of the transcription factor, hypoxic inducible factor-1. Studies in animal models (mutant mice, diet-induced obesity) and cell-culture systems (mouse and human adipocytes) have provided strong support for a role for hypoxia in modulating the production of several inflammation-related adipokines, including increased IL-6, leptin and macrophage migratory inhibition factor production together with reduced adiponectin synthesis. Increased glucose transport into adipocytes is also observed with low O2 tension, largely as a result of the up-regulation of GLUT-1 expression, indicating changes in cellular glucose metabolism. Hypoxia also induces inflammatory responses in macrophages and inhibits the differentiation of preadipocytes (while inducing the expression of leptin). Collectively, there is strong evidence to suggest that cellular hypoxia may be a key factor in adipocyte physiology and the underlying cause of adipose tissue dysfunction contributing to the adverse metabolic milieu associated with obesity.
摘要译文
脂肪组织肿块的扩张是肥胖的显着特征，与低度炎症有关。白色脂肪组织分泌多种脂肪因子，其中许多是炎症介质（如TNFα，IL-1β，IL-6，单核细胞趋化蛋白1）。炎性脂肪因子的产生随肥胖而增加，并且这些脂肪因子与胰岛素抵抗和代谢综合征的发展有关。然而，增加肥胖与炎症之间联系的基础尚不清楚。先前已经提出，由于脂肪细胞肥大损害了来自脉管系统的有效O 2供应，肥胖中脂肪组织内的区域可能发生缺氧，从而通过募集转录因子，缺氧诱导因子-1来激发炎症反应。研究动物模型（突变小鼠，饮食诱导的肥胖症）和细胞培养系统（小鼠和人类脂肪细胞）为缺氧在调节几种炎症相关脂肪因子的产生中的作用提供了强有力的支持，包括增加的IL-6，瘦蛋白和巨噬细胞迁移抑制因子的产生以及降低的脂联素合成。在低O2张力下也观察到葡萄糖向脂肪细胞的转运增加，这主要是由于GLUT-1表达的上调，表明细胞葡萄糖代谢的变化。缺氧还诱导巨噬细胞中的炎症反应并抑制前脂肪细胞的分化（同时诱导瘦蛋白的表达）。总的来说，提示细胞缺氧可能是脂肪细胞生理学的关键因素，也是造成与肥胖有关的不良代谢环境的脂肪组织功能障碍的根本原因。
I. Stuart Wood (a1); Fátima Pérez de Heredia (a1); Bohan Wang (a1);Paul Trayhurn (a1). Cellular hypoxia and adipose tissue dysfunction in obesity: Symposium on ‘Frontiers in adipose tissue biology’[J]. Proceedings of the Nutrition Society, 2009,68(4): 370-377