Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity.
Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity.
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DOI：
10.1371/journal.pone.0019831
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
O'Doherty RM
中科院分区：
文献类型：
--
作者：
Mantell BS;Stefanovic-Racic M;Yang X;Dedousis N;Sipula IJ;O'Doherty RM
自然杀伤T（NKT）细胞在肥胖代谢异常发病机制中的作用存在争议。虽然NKT和CD 8 + T细胞的组合遗传缺失改善了葡萄糖耐量并减少了炎症，但最近的观察结果使这些数据的解释变得复杂，即单独缺失CD 8 + T细胞减少了肥胖诱导的炎症和代谢失调，留下了NKT细胞耗竭的代谢影响问题尚未解决。为了解决这个问题，将缺乏NKT细胞但具有完整的CD 8 + T细胞补体的CD 1d敲除小鼠（CD 1d −/−）和纯C57 BL/6 J背景的同窝野生型对照（WT）暴露于高脂肪饮食，并评估葡萄糖耐受不良、胰岛素抵抗、血脂异常、炎症和肥胖。CD 1d −/−和WT的摄食量（15.5±4.3 vs 15.3±1.8 kcal/小鼠/天）、体重增加（21.8±1.8 vs 22.8±1.4 g）和脂肪量（18.6±1.9 vs 19.5±2.1 g）分别相似。正如从这些数据中预期的那样，代谢率（3.0±0.1 vs 2.9±0.2 ml O2/g/h）和活性（21.6±4.3 vs 18.5±2.6束中断/min）未因NKT细胞耗竭而改变。此外，CD 1d −/−中高脂喂养诱导的胰岛素抵抗、葡萄糖耐受不良、肝脏脂肪变性以及脂肪和肝脏炎症标志物表达（TNFα、IL-6、IL-10、IFN-γ、MCP-1、MIP 1 α）的程度与WT无差异。我们的结论是，删除NKT细胞，在没有改变的CD 8 + T细胞群体，是不足以防止饮食诱导的肥胖症的代谢异常的发展。
The contribution of natural killer T (NKT) cells to the pathogenesis of metabolic abnormalities of obesity is controversial. While the combined genetic deletion of NKT and CD8+ T-cells improves glucose tolerance and reduces inflammation, interpretation of these data have been complicated by the recent observation that the deletion of CD8+ T-cells alone reduces obesity-induced inflammation and metabolic dysregulation, leaving the issue of the metabolic effects of NKT cell depletion unresolved. To address this question, CD1d null mice (CD1d−/−), which lack NKT cells but have a full complement of CD8+ T-cells, and littermate wild type controls (WT) on a pure C57BL/6J background were exposed to a high fat diet, and glucose intolerance, insulin resistance, dyslipidemia, inflammation, and obesity were assessed. Food intake (15.5±4.3 vs 15.3±1.8 kcal/mouse/day), weight gain (21.8±1.8 vs 22.8±1.4 g) and fat mass (18.6±1.9 vs 19.5±2.1 g) were similar in CD1d−/− and WT, respectively. As would be expected from these data, metabolic rate (3.0±0.1 vs 2.9±0.2 ml O2/g/h) and activity (21.6±4.3 vs 18.5±2.6 beam breaks/min) were unchanged by NKT cell depletion. Furthermore, the degree of insulin resistance, glucose intolerance, liver steatosis, and adipose and liver inflammatory marker expression (TNFα, IL-6, IL-10, IFN-γ, MCP-1, MIP1α) induced by high fat feeding in CD1d−/− were not different from WT. We conclude that deletion of NKT cells, in the absence of alterations in the CD8+ T-cell population, is insufficient to protect against the development of the metabolic abnormalities of diet-induced obesity.
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影响因子：
13.5
作者：
Guebre-Xabier, M;Yang, SQ;Diehl, AM
通讯作者：
Diehl, AM
影响因子：
7.3
作者：
Elinav, E;Pappo, O;Ilan, Y
通讯作者：
Ilan, Y
影响因子：
5
作者：
Yang, Liu;Jhaveri, Ravi;Diehl, Anna Mae
通讯作者：
Diehl, Anna Mae
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
DOI：
10.1152/ajpendo.00497.2007
发表时间：
2008-05-01
影响因子：
5.1
作者：
Stefanovic-Racic, Maja;Perdomo, German;O'Doherty, Robert M.
通讯作者：
O'Doherty, Robert M.