IL-1 and LPS but not IL-6 inhibit differentiation and downregulate PPAR gamma in brown adipocytes
IL-1 and LPS but not IL-6 inhibit differentiation and downregulate PPAR gamma in brown adipocytes
复制标题
DOI：
10.1016/j.cyto.2003.12.001
复制
发表时间：
2004-04-07
期刊：
影响因子：
3.8
通讯作者：
Houstek, J
中科院分区：
文献类型：
--
作者：
Mrácek, T;Cannon, B;Houstek, J
棕色脂肪组织（BAT）是啮齿类动物和所有幼年哺乳动物的产热器官。有很好的实验证据表明，其产热活性在发热过程中也起作用，并且这种激活仅通过肾上腺素能途径介导。然而，我们已经表明，棕色脂肪细胞高度表达致热因子（IL-1，LPS）的受体，并且在其活化后，棕色脂肪细胞能够通过产生IL-6和IL-1 α来响应。在这项研究中，我们研究了致热原（IL-1 β、IL-6和LPS）长期处理原代培养的小鼠棕色脂肪细胞对其分化为成熟脂肪细胞能力的影响。我们发现，用IL-1 β或LPS处理，而不是用IL-6处理，抑制棕色脂肪细胞的分化，这伴随着PPARgamma mRNA减少2.5 - 10倍。因此，IL-1 β和LPS的抗脂肪形成作用可以通过下调PPARgamma水平来介导，类似于另一种致热细胞因子-TNF α的抗脂肪形成作用。我们还发现，用IL-1或LPS预处理棕色脂肪细胞导致更明显的（2 - 4倍）诱导IL-6转录后，整个24小时的时间过程中的肾上腺素能刺激。这些结果支持这样的观点，即BAT功能不仅作为效应器，而且作为发热反应的介质;而产热活性与终末分化细胞，早期发育状态的棕色脂肪细胞似乎能够发挥调解作用。(C)2004爱思唯尔有限公司保留所有权利。
Brown adipose tissue (BAT) is well recognized as a heat-producing organ of rodents and generally all young mammals. There is good experimental evidence that its thermogenic activity plays a role also during development of fever and that this activation is mediated exclusively via an adrenergic pathway. However, we have shown that brown adipocytes highly express receptors for pyrogenic factors (IL-1, LPS) and that after their activation, brown adipocytes are capable of responding by production of IL-6 and IL-1alpha. In this study we examined the effect of chronic treatment of mouse brown adipocytes in primary culture with pyrogens (IL-1beta IL-6 and LPS) on their ability to differentiate into mature adipocytes. We found that treatment with IL-1beta or LPS, but not with IL-6, inhibited the differentiation of brown adipocytes, which was accompanied by a 2.5-10-fold decrease in PPARgamma mRNA. The anti-adipogenic effect of IL-1beta and LPS could thus be mediated via downregulation of PPARgamma levels, similar to the anti-adipogenic action of another pyrogenic cytokine-TNFalpha. We also found that pretreatment of brown adipocytes with IL-1 or LPS led to a more pronounced (2-4-fold) induction of IL-6 transcripts upon whole 24 h time course of adrenergic stimulation. These results support the view that BAT functions not only as an effector but also as a mediator of the febrile response; while the thermogenic activity is associated with terminally differentiated cells, earlier developmental states of brown adipocytes seem to be able to play a mediatory role. (C) 2004 Elsevier Ltd. All rights reserved.