Pro-inflammatory cytokines and adipose tissue
Pro-inflammatory cytokines and adipose tissue
复制标题
DOI：
10.1079/pns2001110
复制
发表时间：
2001-08-01
影响因子：
7
通讯作者：
Coppack, SW
中科院分区：
文献类型：
--
作者：
Coppack, SW
细胞因子似乎是脂肪组织新陈代谢的主要调节因子。细胞因子系统的治疗调节提供了脂肪组织行为发生重大改变的可能性。脂肪组织中的细胞因子来源于脂肪细胞、前脂肪细胞和其他类型的细胞。基因表达研究表明，脂肪细胞既能合成肿瘤坏死因子α，又能合成多种白介素类，尤其是IL-1β和IL-6。其他具有免疫功能的脂肪细胞产品包括补体系统产品和巨噬细胞集落刺激因子。脂肪细胞内的细胞因子分泌似乎与其他细胞相似。人们普遍认为，肥胖患者循环中的肿瘤坏死因子-α和白介素6浓度略有升高。大多数研究表明，肥胖受试者的脂肪组织在体外增加了肿瘤坏死因子-α的表达或分泌。调节脂肪组织内细胞因子释放的因素似乎包括常见的“炎性”刺激，如脂多糖，但也包括脂肪细胞本身的大小和儿茶酚胺。关于胰岛素和皮质醇是否调节肿瘤坏死因子-α，存在相互矛盾的数据。脂肪组织中细胞因子的影响包括一些可以被描述为新陈代谢的行为。肿瘤坏死因子-α和白介素6抑制脂蛋白脂肪酶，肿瘤坏死因子-α还能刺激激素敏感的脂肪酶，诱导解偶联蛋白表达。肿瘤坏死因子-α还通过影响葡萄糖转运蛋白4、胰岛素受体自身磷酸化和胰岛素受体底物-1来下调胰岛素刺激的葡萄糖摄取。所有这些作用都会减少脂肪组织中的脂肪堆积。其他的作用似乎更“营养”，包括诱导细胞凋亡、调节细胞大小和诱导去分化(后者涉及减少的过氧化物体增殖物激活的受体伽马)。细胞因子是其他细胞因子的重要刺激因子和抑制因子。此外，细胞因子似乎还调节其他调节系统。后者的例子包括对瘦素分泌的影响(可能是刺激后抑制)和β(3)肾上腺素受体表达的减少。对于哪些来自脂肪组织的细胞因子起远程调节作用，即激素，似乎没有明确的共识。瘦素在结构上是一种细胞因子，也是一种激素。IL-6似乎是由脂肪组织系统性地释放的，但肿瘤坏死因子-α可能不是。瘦素和IL-6似乎都作用于下丘脑，IL-6作用于肝脏，而瘦素可能作用于胰腺。免疫系统在全身能量平衡中的重要性为细胞因子和脂肪组织之间的联系提供了理论基础。很明显，肿瘤坏死因子-α是一种强大的脂肪组织自分泌和旁分泌调节因子。其他细胞因子，特别是瘦素，可能还有IL-6，对脂肪组织的作用较小。这些细胞因子起荷尔蒙的作用，报告脂肪组织在全身储存的状态。
Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor alpha (TNF-alpha) and several interleukins (IL), notably IL-1 beta and IL-6. Other adipocyte products with 'immunological' actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-alpha and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-alpha mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual 'inflammatory' stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-alpha. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-alpha and IL-6 inhibit lipoprotein lipase, and TNF-alpha additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-alpha also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more 'trophic', and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor gamma). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of beta (3)-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-alpha is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-alpha is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.