Intrinsic Properties of Brown and White Adipocytes Have Differential Effects on Macrophage Inflammatory Responses.

Intrinsic Properties of Brown and White Adipocytes Have Differential Effects on Macrophage Inflammatory Responses.
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DOI:
10.1155/2017/9067049
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发表时间:
2017
影响因子:
4.6
通讯作者:
Sarangarajan R
Sarangarajan R
中科院分区:
医学3区
文献类型:
--
作者:
Dowal L;Parameswaran P;Phat S;Akella S;Majumdar ID;Ranjan J;Shah C;Mogre S;Guntur K;Thapa K;Gesta S;Vishnudas VK;Narain NR;Sarangarajan R

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肥胖的特征是慢性、低级别的炎症。在这里,我们研究了白色和棕色脂肪细胞之间的内在差异是否会影响巨噬细胞的炎症状态。白色和棕色脂肪细胞的特征是UCP-1、Pgc1α、Pgc1β和CIDEA的转录调节以及IL-6的分泌水平。在PMA分化的U937和THP-1巨噬细胞与白色和棕色脂肪细胞单独或间接共同培养后,通过检测IL-6的分泌和一组炎症基因的转录调控来评估静息状态下和在脂多糖/干扰素-γ和IL-4刺激后的炎症情况。与棕色脂肪细胞相比,白色脂肪细胞的单一培养显示IL-6的分泌增加。白色脂肪细胞与U937和THP-1巨噬细胞共培养比棕色脂肪细胞与这两种巨噬细胞共培养更能诱导IL-6的分泌。与巨噬细胞共培养的白色脂肪细胞增加了两种类型的炎症基因的表达。相反,与棕色脂肪细胞共培养的巨噬细胞诱导炎症基因表达下调或没有变化。脂肪细胞对巨噬细胞的影响似乎与刺激状态无关。棕色脂肪细胞显示出抑制巨噬细胞炎症的内在能力,而白色脂肪细胞则增强了这种能力。这些数据表明,棕色脂肪细胞可能不太容易发生与肥胖有关的脂肪组织炎症。
Obesity is marked by chronic, low-grade inflammation. Here, we examined whether intrinsic differences between white and brown adipocytes influence the inflammatory status of macrophages. White and brown adipocytes were characterized by transcriptional regulation of UCP-1, PGC1α, PGC1β, and CIDEA and their level of IL-6 secretion. The inflammatory profile of PMA-differentiated U937 and THP-1 macrophages, in resting state and after stimulation with LPS/IFN-gamma and IL-4, was assessed by measuring IL-6 secretion and transcriptional regulation of a panel of inflammatory genes after mono- or indirect coculture with white and brown adipocytes. White adipocyte monocultures show increased IL-6 secretion compared to brown adipocytes. White adipocytes cocultured with U937 and THP-1 macrophages induced a greater increase in IL-6 secretion compared to brown adipocytes cocultured with both macrophages. White adipocytes cocultured with macrophages increased inflammatory gene expression in both types. In contrast, macrophages cocultured with brown adipocytes induced downregulation or no alterations in inflammatory gene expression. The effects of adipocytes on macrophages appear to be independent of stimulation state. Brown adipocytes exhibit an intrinsic ability to dampen inflammatory profile of macrophages, while white adipocytes enhance it. These data suggest that brown adipocytes may be less prone to adipose tissue inflammation that is associated with obesity.