Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat
Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat
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DOI：
10.4049/jimmunol.1201272
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发表时间：
2012-09-01
影响因子：
4.4
通讯作者：
Serhan, Charles N.
中科院分区：
文献类型：
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作者：
Claria, Joan;Dalli, Jesmond;Serhan, Charles N.
肥胖和肥胖相关疾病患病率的空前增加与脂肪组织中的慢性低度炎症状态有因果关系。及时解决炎症和恢复该组织的稳态是减少肥胖引起的代谢功能障碍的关键。在这项研究中，与发炎的脂肪，我们调查的生物合成，转化，和行动的Resolvins D1（RvD 1，7S，8 R，17 S-三羟基-4Z，9 E，11 E，13 Z，15 E，19 Z-二十二碳六烯酸）和D2（RvD 2，7S，16 R，17 S-三羟基-4Z，8 E，10 Z，12 E，14 E，19 Z-二十二碳六烯酸），有效的抗炎和促分解脂质介质（LM），以及它们调节单核细胞与脂肪细胞相互作用的能力。脂质介质代谢脂质组学从人和小鼠脂肪组织的内源性来源中鉴定出RvD 1和RvD 2。我们还鉴定了前分辨受体（即，ALX/FPR 2、ChemR 23和GPR 32）。与瘦肉组织相比，肥胖脂肪组织缺乏这些内源性抗炎信号。对于发炎的肥胖脂肪组织，RvD 1和RvD 2各自以时间和浓度依赖性方式挽救受损的脂联素表达和分泌，以及减少促炎脂肪因子的产生，包括瘦素、TNF-α、IL-6和IL-1 β。RvD 1和RvD 2分别减少MCP-1和白三烯B-4刺激的单核细胞与脂肪细胞的粘附及其跨脂肪迁移。脂肪组织迅速将两种消退素（Rvs）转化为新型氧代Rvs。RvD 2被酶促转化为7-氧代-RvD 2作为其主要代谢途径，保留脂肪定向的RvD 2作用。这些结果表明，在脂肪中，D-系列Rvs（RvD 1和RvD 2）是有效的促消退介质，可以抵消肥胖诱导的脂肪炎症中局部脂肪因子的产生和单核细胞的积累。免疫学杂志，2012，189：2597-2605。
The unprecedented increase in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. In this study, with inflamed adipose, we investigated the biosynthesis, conversion, and actions of Resolvins D1 (RvD1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) and D2 (RvD2, 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), potent anti-inflammatory and proresolving lipid mediators (LMs), and their ability to regulate monocyte interactions with adipocytes. Lipid mediator-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified proresolving receptors (i.e., ALX/FPR2, ChemR23, and GPR32) in these tissues. Compared with lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner as well as decreasing proinflammatory adipokine production including leptin, TNF-alpha, IL-6, and IL-1 beta. RvD1 and RvD2 each reduced MCP-1 and leukotriene B-4-stimulated monocyte adhesion to adipocytes and their trans-adipose migration. Adipose tissue rapidly converted both resolvins (Rvs) to novel oxo-Rvs. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series Rvs (RvD1 and RvD2) are potent proresolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation. The Journal of Immunology, 2012, 189: 2597-2605.