Altered signalling and gene expression associated with the immune system and the inflammatory response in obesity
Altered signalling and gene expression associated with the immune system and the inflammatory response in obesity
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DOI：
10.1017/s0007114507838050
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发表时间：
2007-10-01
影响因子：
3.6
通讯作者：
Canete, Ramon
中科院分区：
文献类型：
--
作者：
Gil, Angel;Maria Aguilera, Concepcion;Canete, Ramon
白色脂肪组织不仅作为能量储存器官，而且作为重要的内分泌器官，参与许多病理过程的调节。肥胖状态的特征是低度全身炎症，这主要是脂肪细胞以及脂肪驻留和募集巨噬细胞活性增加的结果。在过去的几年中，人们对脂肪组织的各种产物（包括脂肪因子和细胞因子）进行了表征，并确定了许多将脂肪组织代谢与免疫系统联系起来的途径。在肥胖中，脂肪因子和细胞因子通过细胞内信号通路的促炎和抗炎作用主要涉及核因子 kappa B (NF-kappa B) 和 Jun N 末端激酶 (INK) 系统以及 I kappa B 激酶 beta (IKK-beta)。丝裂原激活蛋白激酶 (MAPK) 和细胞外信号调节激酶 (ERK) 途径可导致信号转导器和转录激活剂 3 (STAT3) 激活，在促炎细胞因子的产生中也很重要。肥胖会增加脂肪组织中瘦素和其他细胞因子以及一些巨噬细胞和炎症标志物的表达，并降低脂联素的表达。许多细胞因子，例如肿瘤坏死因子 α (TNF-α) 和单核细胞趋化蛋白 I (MCP-1) 以及一些促炎白细胞介素、白细胞抗原、趋化因子、表面粘附分子和金属蛋白酶上调，而其他因子下调。本文将重点关注肥胖和炎症之间的分子机制，重点关注脂肪细胞成分中信号传导和基因表达的改变。
White adipose tissue functions not only as an energy store but also as an important endocrine organ and is involved in the regulation of many pathological processes. The obese state is characterised by a low-grade systemic inflammation, mainly a result of increased adipocyte as well as fat resident- and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. In obesity, the pro- and anti-inflammatory effects of adipokines and cytokines through intracellular signalling pathways mainly involve the nuclear factor kappa B (NF-kappa B) and the Jun N-terminal kinase (INK) systems as well as the I kappa B kinase beta (IKK-beta). Mitogen-activated protein kinase (MAPK) and extracellular-signal-regulated kinase (ERK) pathways, which lead to signal transducer and activator of transcription 3 (STAT3) activation, are also important in the production of pro-inflammatory cytokines. Obesity increases the expression of leptin and other cytokines, as well as some macrophage and inflammatory markers, and decreases adiponectin expression in adipose tissue. A number of cytokines, e.g. tumour necrosis factor alpha (TNF-alpha) and monocyte chemotactic protein I (MCP-1), and some pro-inflammatory interleukins, leuckocyte antigens, chemochines, surface adhesion molecules and metalloproteases are up-regulated whereas other factors are down-regulated. The present paper will focus on the molecular mechanisms linking obesity and inflammation with emphasis on the alteration of signalling and gene expression in adipose cell components.