Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.
Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.
复制标题
DOI：
10.1016/j.cmet.2014.03.029
复制
发表时间：
2014-05-06
期刊：
影响因子：
29
通讯作者：
Murphy AJ
中科院分区：
文献类型：
--
作者：
Nagareddy PR;Kraakman M;Masters SL;Stirzaker RA;Gorman DJ;Grant RW;Dragoljevic D;Hong ES;Abdel-Latif A;Smyth SS;Choi SH;Korner J;Bornfeldt KE;Fisher EA;Dixit VD;Tall AR;Goldberg IJ;Murphy AJ
肥胖与巨噬细胞向脂肪组织(AT)的渗透有关，从而导致胰岛素抵抗和糖尿病。然而，关于AT巨噬细胞(ATM)的起源，人们知之甚少。我们发现肥胖小鼠模型有显著的单核细胞增多症和中性粒细胞增多症，与骨髓(BM)髓系祖细胞的增殖和扩张有关。在移植时，瘦受者的骨髓祖细胞增殖，而小鼠和人类的体重减轻(通过胃旁路)与单核细胞增多和中性粒细胞增多的逆转有关。脂肪S100A8/A9诱导ATMTLR4/MyD88和NLRP3炎症性依赖的IL-1β的产生。IL-1β与骨髓髓系祖细胞上的IL-1受体(IL-1R)相互作用，刺激单核细胞和中性粒细胞的产生。这些研究揭示了ATM和BM髓系祖细胞之间的正反馈回路，提示抑制TLR4L或NLRP3-IL-1β信号轴可以减轻肥胖患者的AT炎症和胰岛素抵抗。
Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transplantation conferred myeloid progenitor proliferation in lean recipients, while weight loss in both mice and humans (via gastric bypass) was associated with a reversal of monocytosis and neutrophilia. Adipose S100A8/A9 induced ATM TLR4/MyD88 and NLRP3 inflammasome-dependent IL-1β production. IL-1β interacted with the IL-1 receptor (IL-1R) on BM myeloid progenitors to stimulate the production of monocytes and neutrophils. These studies uncover a positive feedback loop between ATMs and BM myeloid progenitors, and suggest that inhibition of TLR4 ligands or the NLRP3-IL-1β signaling axis could reduce AT inflammation and insulin resistance in obesity.
登录
查看更多内容
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
影响因子：
4
作者：
Klebanov, S;Astle, CM;Harrison, DE
通讯作者：
Harrison, DE
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R