PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice.
PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice.
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DOI：
10.1186/1475-2840-9-64
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发表时间：
2010-10-18
影响因子：
9.3
通讯作者：
Kintscher U
中科院分区：
文献类型：
--
作者：
Foryst-Ludwig A;Hartge M;Clemenz M;Sprang C;Hess K;Marx N;Unger T;Kintscher U
脂肪组织（AT）炎症最近已被接受为肥胖介导的胰岛素抵抗的第一步。我们以前可以表明，高脂饮食（HFD）喂养的小鼠发生全身性胰岛素抵抗（IR）和葡萄糖耐受不良（GI）与CD 4阳性T淋巴细胞浸润到内脏AT。当富含AT时，这些T淋巴细胞参与脂肪组织炎症的发展和随后的促炎巨噬细胞的募集。本研究的目的是阐明胰岛素增敏PPARgamma在IR形成过程中对T淋巴细胞浸润的作用，并比较罗格列酮和替米沙坦在小鼠饮食诱导肥胖模型（DIO模型）中PPARgamma介导的抗炎作用。为了研究全身性胰岛素抵抗和葡萄糖耐受不良早期发生的分子机制，雄性C57 BL/6 J小鼠喂食高脂饲料（HFD）10周，同时接受罗格列酮、替米沙坦或溶剂的药物干预。通过T细胞标志物CD 3 γ和趋化因子SDF 1 α的定量分析，罗格列酮和替米沙坦均能减少T淋巴细胞浸润AT。随后，两种PPARgamma激动剂都能够减弱巨噬细胞浸润到AT中，通过MCP 1和F4/80表达的减少来测量。在AT炎症减少的同时，配体活化的PPARgamma改善了饮食诱导的IR和GI。总之，本研究表明，在AT中，PPARgamma介导的抗炎作用与葡萄糖代谢的全身改善之间存在密切联系，确定T淋巴细胞是PPARgamma作用的一种细胞介质。
Inflammation of adipose tissue (AT) has been recently accepted as a first step towards obesity-mediated insulin resistance. We could previously show that mice fed with high fat diet (HFD) develop systemic insulin resistance (IR) and glucose intolerance (GI) associated with CD4-positive T-lymphocyte infiltration into visceral AT. These T-lymphocytes, when enriched in AT, participate in the development of fat tissue inflammation and subsequent recruitment of proinflammatory macrophages. The aim of this work was to elucidate the action of the insulin sensitizing PPARgamma on T-lymphocyte infiltration during development of IR, and comparison of the PPARgamma-mediated anti-inflammatory effects of rosiglitazone and telmisartan in diet-induced obesity model (DIO-model) in mice. In order to investigate the molecular mechanisms underlying early development of systemic insulin resistance and glucose intolerance male C57BL/6J mice were fed with high fat diet (HFD) for 10-weeks in parallel to the pharmacological intervention with rosiglitazone, telmisartan, or vehicle. Both rosiglitazone and telmisartan were able to reduce T-lymphocyte infiltration into AT analyzed by quantitative analysis of the T-cell marker CD3gamma and the chemokine SDF1alpha. Subsequently, both PPARgamma agonists were able to attenuate macrophage infiltration into AT, measured by the reduction of MCP1 and F4/80 expression. In parallel to the reduction of AT-inflammation, ligand-activated PPARgamma improved diet-induced IR and GI. Together the present study demonstrates a close connection between PPARgamma-mediated anti-inflammation in AT and systemic improvement of glucose metabolism identifying T-lymphocytes as one cellular mediator of PPARgamma´s action.
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影响因子：
8.3
作者：
Walcher, Daniel;Hess, Katharina;Marx, Nikolaus
通讯作者：
Marx, Nikolaus
影响因子：
4.3
作者：
Bassaganya-Riera, Josep;Misyak, Sarah;Hontecillas, Raquel
通讯作者：
Hontecillas, Raquel
影响因子：
5.8
作者：
Bruun, JM;Lihn, AS;Richelsen, B
通讯作者：
Richelsen, B
影响因子：
7.7
作者：
Schupp, M;Clemenz, M;Kintscher, U
通讯作者：
Kintscher, U
影响因子：
4.4
作者：
Clark, RB;Bishop-Bailey, D;Padula, SJ
通讯作者：
Padula, SJ