Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro
Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro
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DOI：
10.1016/s0303-7207(02)00007-2
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发表时间：
2002-04-25
影响因子：
4.1
通讯作者：
Richelsen, B
中科院分区：
文献类型：
--
作者：
Bruun, JM;Pedersen, SB;Richelsen, B
瘦素在脂肪细胞中合成，主要通过中枢途径抑制食欲并增加啮齿动物和人类的代谢率。最近也有人提出瘦素具有外周效应，并参与胰岛素的不良作用。由于细胞因子和趋化因子可能对食欲调节以及一些肥胖相关的并发症如胰岛素抵抗和心血管疾病有影响，我们研究了各种细胞因子和趋化因子对体外人脂肪组织片段中瘦素产生的影响。将来自健康正常至超重女性的腹部皮下脂肪组织与细胞因子：肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1 β）以及趋化因子：白细胞介素-8（IL-8）孵育高达48 μ L。IL-1 β（50 ng/ml）和TNF-α（10 ng/ml）使瘦素产生减少30- 50%（P < 0.05），基因表达减少80- 90%（P < 0.05）。相反，IL-6和IL-8对瘦素产生或瘦素基因表达没有影响。有趣的是，IL-1 β引起了一个双相效应的瘦素释放与增量相内观察到4小时内没有伴随的变化，瘦素基因表达，其次是一个持久的抑制瘦素释放和瘦素基因表达。这可能表明IL-1 β通过翻译后途径诱导瘦素分泌的急性增加，可能是通过从脂肪组织内预先形成的池中释放瘦素。瘦素分泌和转录的长期减少可能表明促炎细胞因子如IL-1 β和TNF-α可能影响循环瘦素水平，从而影响脂肪组织到脑的信号传导，这可能与肥胖相关疾病如胰岛素抵抗和心血管疾病有关。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Leptin is synthesized in adipocytes and acts primarily through central pathways suppressing appetite and increasing the metabolic rate in rodents as well as in humans. Recently leptin has also been suggested to have peripheral effects and be involved ill insulin action. Since cytokines and chemokines may have effects on appetite regulation as well as on some of the obesity-related complications e.g. insulin resistance and cardiovascular disease, we investigated the effects of various cytokines and chemokines on leptin production in human adipose tissue fragments in vitro. Abdominal subcutaneous adipose tissue from healthy normal to overweight females was incubated for up to 48 It with the cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) and the chemokine: interleukin-8 (IL-8). IL-1beta (50 ng/ml) and TNF-alpha, (10 ng/ml) decreased leptin production by 30-50%, (P < 0.05) and gene expression by 80-90%, (P < 0.05). In contrast, IL-6 and IL-8 had no effect on either leptin production or leptin gene expression. Interestingly, IL-1beta elicited a biphasic effect on leptin release with an incremental phase observed within 4 h with no concomitant change in leptin gene expression, followed by a long-lasting inhibition of leptin release and leptin gene expression. This could suggest that IL-1beta through a post-translational pathway induced an acute increase in leptin-secretion, perhaps through the release of leptin from a pre-formed pool within the adipose tissue. The long-term decrease in both leptin secretion and transcription could indicate that pro-inflammatory cytokines such as IL-1beta and TNF-alpha might influence the circulating leptin levels and thereby influence the adipose tissue to brain signalling, which could be of importance in relation to the obesity-associated diseases such as insulin resistance and cardiovascular disease. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.