Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding.
Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding.
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DOI：
10.1161/circresaha.108.182998
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发表时间：
2009-02-27
影响因子：
20.1
通讯作者：
Weintraub NL
中科院分区：
文献类型：
--
作者：
Chatterjee TK;Stoll LL;Denning GM;Harrelson A;Blomkalns AL;Idelman G;Rothenberg FG;Neltner B;Romig-Martin SA;Dickson EW;Rudich S;Weintraub NL
脂肪组织贮库起源于不同的前体细胞，功能多样，并以贮库特异性方式调节疾病过程。然而，血管周围脂肪细胞的功能特性及其对血管壁疾病的影响仍有待确定。我们发现，人冠状动脉血管周围脂肪细胞表现出减少的脂肪细胞分化的状态相比，来自皮下和内脏（肾周）的脂肪库。在血管周围脂肪细胞中，抗炎脂联素的分泌显著减少，而促炎细胞因子IL-6、IL-8和MCP-1的分泌显著增加。脂肪细胞功能的这些贮库特异性差异在新鲜分离的脂肪组织和体外分化的脂肪细胞中均是可证实的。与皮下和内脏脂肪组织相比，小鼠主动脉弓血管周围脂肪组织同样表达较低水平的脂肪细胞相关基因。此外，两周的高脂肪喂养导致血管周围脂肪组织中脂肪细胞相关基因表达进一步减少，同时上调促炎基因表达。在没有巨噬细胞募集到血管周围脂肪库的情况下观察到这些变化。我们的结论是，血管周围脂肪细胞表现出减少的分化和提高促炎状态，属性是内在的脂肪细胞居住在这个仓库。由脂肪喂养引起的血管周围脂肪组织功能障碍表明，这种独特的脂肪库能够将代谢信号与血管壁中的炎症联系起来。
Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of anti-inflammatory adiponectin is markedly reduced, whereas that of pro-inflammatory cytokines IL-6, IL-8, and MCP-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, two weeks of high fat feeding caused further reductions in adipocyte-associated gene expression, while up-regulating pro-inflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened pro-inflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.