Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation.
Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation.
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DOI：
10.1016/j.cmet.2013.11.001
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发表时间：
2013-12-03
期刊：
影响因子：
29
通讯作者：
Ferrante AW Jr
中科院分区：
文献类型：
--
作者：
Xu X;Grijalva A;Skowronski A;van Eijk M;Serlie MJ;Ferrante AW Jr
肥胖会激活复杂的全身免疫反应，包括向关键代谢组织募集巨噬细胞和其他免疫细胞。目前的模型假设肥胖和过量的脂质典型地激活巨噬细胞，使它们向M1（炎症）状态极化。关于脂肪组织巨噬细胞（ATMs）的非炎症功能知之甚少。在这里，我们表明脂肪组织（AT）在肥胖模型中的扩张诱导了ATMs中溶酶体的生物生成程序，并与脂质分解代谢有关，但不是典型的炎症表型。该程序由AT产生的因子诱导，并与atm的脂质积累紧密耦合。抑制ATM溶酶体功能会损害ATM的脂质代谢，增加ATM的脂质含量，减少整个ATM的脂解。这些数据表明，atm定量地促进了肥胖诱导炎症的发展，但也在脂质运输中发挥重要作用，而不依赖于它们的炎症表型。
Obesity activates a complex systemic immune response that includes the recruitment of macrophages and other immune cells to key metabolic tissues. Current models postulate that obesity and excess lipids classically activate macrophages, polarizing them toward an M1 (inflammatory) state. Little is known about noninflammatory functions of adipose tissue macrophages (ATMs). Here, we show that the expansion of adipose tissue (AT) across models of obesity induces a program of lysosome biogenesis in ATMs and is associated with lipid catabolism but not a classic inflammatory phenotype. This program is induced by factors produced by AT and is tightly coupled to lipid accumulation by ATMs. Inhibition of ATM lysosome function impairs lipid metabolism and increases lipid content in ATMs and reduces whole AT lipolysis. These data argue that ATMs contribute quantitatively to the development of obesity-induced inflammation but also serve an important role in lipid trafficking independent of their inflammatory phenotype.
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影响因子：
64.8
作者：
Nguyen, Khoa D.;Qiu, Yifu;Cui, Xiaojin;Goh, Y. P. Sharon;Mwangi, Julia;David, Tovo;Mukundan, Lata;Brombacher, Frank;Locksley, Richard M.;Chawla, Ajay
通讯作者：
Chawla, Ajay
DOI：
10.1038/nri2528
发表时间：
2009-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
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：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
82.9
作者：
Talukdar, Saswata;Oh, Da Young;Bandyopadhyay, Gautam;Li, Dongmei;Xu, Jianfeng;McNelis, Joanne;Lu, Min;Li, Pingping;Yan, Qingyun;Zhu, Yimin;Ofrecio, Jachelle;Lin, Michael;Brenner, Martin B.;Olefsky, Jerrold M.
通讯作者：
Olefsky, Jerrold M.