T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice.
T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice.
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DOI：
10.1038/oby.2010.1
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Obin MS
中科院分区：
文献类型：
--
作者：
Strissel KJ;DeFuria J;Shaul ME;Bennett G;Greenberg AS;Obin MS
获得性免疫在肥胖相关脂肪组织（AT）炎症和胰岛素抵抗（IR）中的作用存在争议。我们采用流式细胞术和定量PCR来评估在4-22周的高（60%能量）脂肪饮食（HFD）期间C57 BL/6小鼠附睾AT（eAT）中的T细胞募集和活化。到第6周，喂食HFD的小鼠中eAT质量和基质血管细胞（SVC）数量增加了3倍，与IR的发作一致。我们观察到在HFD的前16周期间，CD 3 + SVC的比例或CD 3、IFNγ或活化后调节的正常T细胞表达和分泌（RANTES）的基因表达没有增加。相比之下，CD 11 c+巨噬细胞（Mφ）在第8周富集6倍（p < 0.01）。HFD 20-22周时检测到SVC对T细胞（主要是CD 4+和CD 8+）的富集以及IFNγ和RANTES基因表达的升高（p < 0.01），与eAT重塑的消退一致。HFD诱导的T细胞在肥胖时程中较早引发通过在第12周时eAT中升高的（5倍）IL-12 p40基因表达（p ≤ 0.01）以及在第6周（1倍，p = 0.08）和第12周（5倍，p < 0.001）时PMA/离子载体刺激的eAT外植体的更大IFNγ分泌来表明。总之，T细胞富集和IFNγ基因诱导发生在ATMφ募集、IR发作和eAT重塑消退之后。然而，IFNγ产生的增强引发表明CD 4+和/或CD 8+效应物对促进HFD诱导的AT炎症和IR的细胞介导的免疫应答的贡献。
The role of adaptive immunity in obesity-associated adipose tissue (AT) inflammation and insulin resistance (IR) is controversial. We employed flow cytometry and quantitative PCR to assess T-cell recruitment and activation in epididymal AT (eAT) of C57BL/6 mice during 4–22 weeks of a high (60% energy) fat diet (HFD). By week 6, eAT mass and stromal vascular cell (SVC) number increased 3-fold in mice fed HFD, coincident with onset of IR. We observed no increase in the proportion of CD3+ SVCs or in gene expression of CD3, IFNγ, or regulated upon activation, normal T-cell expressed and secreted (RANTES) during the first 16 weeks of HFD. In contrast, CD11c+ macrophages (Mφ) were enriched 6-fold by week 8 (p < 0.01). SVC enrichment for T cells (predominantly CD4+ and CD8+) and elevated IFNγ and RANTES gene expression were detected by 20–22 weeks of HFD (p < 0.01), coincident with the resolution of eAT remodeling. HFD-induced T cell priming earlier in the obesity time course is suggested by elevated (5-fold) IL-12p40 gene expression in eAT by week 12 (p ≤ 0.01) and greater IFNγ secretion from PMA/ionophore-stimulated eAT explants at week 6 (1 fold, p = 0.08) and week 12 (5 fold, p < 0.001). In summary, T cell enrichment and IFNγ gene induction occur subsequent to ATMφ recruitment, onset of IR and resolution of eAT remodeling. However, enhanced priming for IFNγ production suggests the contribution of CD4+ and/or CD8+ effectors to cell-mediated immune responses promoting HFD-induced AT inflammation and IR.
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影响因子：
4.9
作者：
O'Rourke, R. W.;Metcalf, M. D.;White, A. E.;Madala, A.;Winters, B. R.;Maizlin, I. I.;Jobe, B. A.;Roberts, C. T., Jr.;Slifka, M. K.;Marks, D. L.
通讯作者：
Marks, D. L.
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
影响因子：
7.7
作者：
Ledoux S;Queguiner I;Msika S;Calderari S;Rufat P;Gasc JM;Corvol P;Larger E
通讯作者：
Larger E
影响因子：
3.7
作者：
Caspar-Bauguil, S.;Cousin, B.;Penicaud, L.
通讯作者：
Penicaud, L.
影响因子：
3.1
作者：
Martinez, Fernando Oneissi;Sica, Antonio;Locati, Massimo
通讯作者：
Locati, Massimo