School of Pharmaceutical Sciences, Jilin University, Changchun, China.
School of Pharmaceutical Sciences, Jilin University, Changchun, China,
Obes Facts. 2020;13(1):86-101. doi: 10.1159/000505343. Epub 2020 Jan 21.
In obese individuals, chronic low-grade inflammation resulting from adipocyte-macrophage interactions is a major cause of adipose tissue dysfunction and metabolic disease. This study investigated the role of MAP kinase phosphatase-5 (MKP-5) in obesity-induced inflammation during macrophage and adipocyte interactions.
High-fat diet-induced obese mice were used to explore the role of MKP-5 in obesity-induced adipose tissue inflammation. Macrophage polarization was determined by inflammatory cytokine expression in MKP-5-overexpressed or -silenced Raw264.7 cells exposed to palmitate (PA) or M1/M2 macrophage inducers. To uncover the role of MKP-5 during macrophage-adipocyte interactions, a coculture system composed of differentiated 3T3-L1 and Raw264.7 cells was employed. MAPK inhibitors were used to investigate the involvement of MAPK signaling.
Increased MKP-5 expression was observed in adipose stromal vascular cells (SVCs) of obese mice. In Raw264.7 cells, MKP-5 promoted the switching of M1 macrophages to an M2 phenotype. Notably, MKP-5 reduced inflammation during the interaction of macrophages and adipocytes. MKP-5 overexpression in primary SVCs attenuated the expression of inflammatory mediators and increased the number of obesity-induced adipose tissue macrophages. MKP-5 suppressed PA-induced inflammation through the inactivation of P38, JNK, and ERK MAPKs.
MKP-5 promotes macrophages to switch from the M1 to the M2 phenotype and is an inflammatory inhibitor involved in obesity-induced adipose tissue inflammation and PA-triggered macrophage inflammation via the P38, JNK, and ERK MAPK pathways. MKP-5 may be developed into a potential therapeutic target for obesity-related diseases, including type 2 diabetes mellitus and insulin resistance.
在肥胖个体中，脂肪细胞与巨噬细胞相互作用导致的慢性低度炎症是脂肪组织功能障碍和代谢疾病的主要原因。本研究探讨了丝裂原活化蛋白激酶磷酸酶-5（MKP-5）在肥胖诱导的巨噬细胞和脂肪细胞相互作用过程中引起炎症的作用。
使用高脂肪饮食诱导的肥胖小鼠来探索 MKP-5 在肥胖诱导的脂肪组织炎症中的作用。通过在 MKP-5 过表达或沉默的 Raw264.7 细胞中表达炎症细胞因子，来确定 MKP-5 在过表达棕榈酸（PA）或 M1/M2 巨噬细胞诱导剂时对巨噬细胞极化的作用。为了揭示 MKP-5 在巨噬细胞-脂肪细胞相互作用过程中的作用，使用由分化的 3T3-L1 和 Raw264.7 细胞组成的共培养系统。使用 MAPK 抑制剂来研究 MAPK 信号通路的参与情况。
肥胖小鼠的脂肪基质血管细胞（SVC）中 MKP-5 表达增加。在 Raw264.7 细胞中，MKP-5 促进 M1 巨噬细胞向 M2 表型转化。值得注意的是，MKP-5 减少了巨噬细胞和脂肪细胞相互作用过程中的炎症。原发性 SVC 中的 MKP-5 过表达减轻了促炎介质的表达，并增加了肥胖诱导的脂肪组织巨噬细胞的数量。MKP-5 通过失活 P38、JNK 和 ERK MAPK 抑制 PA 诱导的炎症。
MKP-5 促进巨噬细胞从 M1 表型向 M2 表型转变，是一种炎症抑制剂，参与肥胖诱导的脂肪组织炎症和 PA 触发的巨噬细胞炎症，通过 P38、JNK 和 ERK MAPK 通路。MKP-5 可能成为治疗肥胖相关疾病（包括 2 型糖尿病和胰岛素抵抗）的潜在治疗靶点。
