Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.
Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.
复制标题
DOI：
10.18632/aging.101288
复制
发表时间：
2017-09-07
期刊：
影响因子：
--
通讯作者：
Yung R
中科院分区：
文献类型：
--
作者：
Ghosh AK;O'Brien M;Mau T;Yung R
脂肪组织（AT）炎症是饮食诱导的肥胖和年龄相关性肥胖中代谢功能障碍的中心机制。饮食诱导的肥胖症的研究已经表征了胎球蛋白A（Fet A）在游离脂肪酸（FFA）介导的TLR 4活化和脂肪组织炎症中的作用。然而，Fet A和TLR 4在衰老相关的脂肪组织炎症中的作用尚不清楚。在目前的研究中，分析C57/B16雄性小鼠的胸腺脂肪垫，我们发现，与来自饮食诱导的肥胖模型的数据相反，来自老年小鼠的脂肪组织具有正常的Fet A和TLR 4表达。有趣的是，与正常对照组相比，老年TLR 4缺陷小鼠的脂肪组织炎症减少。我们进一步证明，在老年TLR 4缺陷小鼠中AT炎症的减少与ER应激受损、自噬活性增强和衰老现象减少有关。重要的是，与年龄匹配的野生型小鼠相比，老年TLR 4缺陷小鼠具有改善的葡萄糖耐量，这表明在老年TLR 4缺陷小鼠中观察到的AT炎症减少具有重要的生理后果。总之，我们目前的研究建立了与饮食诱导的AT炎症不同的衰老相关AT炎症的新方面。我们的研究结果还提供了强有力的证据表明，TLR 4在促进衰老脂肪组织炎症中起着重要作用。
Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation.
登录
查看更多内容
高脂饮食在C57BL/6J小鼠的肝脏之前诱导脂肪组织中的肥胖症炎症。
DOI：
10.18632/aging.100738
发表时间：
2015-04
期刊：
Aging
影响因子：
--
作者：
van der Heijden RA;Sheedfar F;Morrison MC;Hommelberg PP;Kor D;Kloosterhuis NJ;Gruben N;Youssef SA;de Bruin A;Hofker MH;Kleemann R;Koonen DP;Heeringa P
通讯作者：
Heeringa P
DOI：
10.18632/aging.101083
发表时间：
2016-10-24
期刊：
Aging
影响因子：
--
作者：
Ghosh AK;Mau T;O'Brien M;Garg S;Yung R
通讯作者：
Yung R
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
7.7
作者：
Abe T;Hirasaka K;Kagawa S;Kohno S;Ochi A;Utsunomiya K;Sakai A;Ohno A;Teshima-Kondo S;Okumura Y;Oarada M;Maekawa Y;Terao J;Mills EM;Nikawa T
通讯作者：
Nikawa T
影响因子：
7.7
作者：
Stefan, Norbert;Fritsche, Andreas;Weikert, Cornelia;Boeing, Heiner;Joost, Hans-Georg;Haring, Hans-Ulrich;Schulze, Matthias B.
通讯作者：
Schulze, Matthias B.