The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity
Objective: 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 macrophag...
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doaj-8c02ddab05214d8291d00ffb08a3163b2020-11-25T03:19:24ZengKarger PublishersObesity Facts1662-40251662-40332020-01-011318610110.1159/000505343505343The Role of MKP-5 in Adipocyte-Macrophage Interactions during ObesityYuanhua LuJie MaJianan ZhaoZhuoyao SongChao ZhouXiu LiuWenjing TengWei WangQi ZhangWeiqun YanPing JiaoObjective: 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. Methods: 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. Results: 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. Conclusions: 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.https://www.karger.com/Article/FullText/505343inflammationmkp-5obesitymacrophageadipocytes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuanhua Lu Jie Ma Jianan Zhao Zhuoyao Song Chao Zhou Xiu Liu Wenjing Teng Wei Wang Qi Zhang Weiqun Yan Ping Jiao |
spellingShingle |
Yuanhua Lu Jie Ma Jianan Zhao Zhuoyao Song Chao Zhou Xiu Liu Wenjing Teng Wei Wang Qi Zhang Weiqun Yan Ping Jiao The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity Obesity Facts inflammation mkp-5 obesity macrophage adipocytes |
author_facet |
Yuanhua Lu Jie Ma Jianan Zhao Zhuoyao Song Chao Zhou Xiu Liu Wenjing Teng Wei Wang Qi Zhang Weiqun Yan Ping Jiao |
author_sort |
Yuanhua Lu |
title |
The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity |
title_short |
The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity |
title_full |
The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity |
title_fullStr |
The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity |
title_full_unstemmed |
The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity |
title_sort |
role of mkp-5 in adipocyte-macrophage interactions during obesity |
publisher |
Karger Publishers |
series |
Obesity Facts |
issn |
1662-4025 1662-4033 |
publishDate |
2020-01-01 |
description |
Objective: 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. Methods: 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. Results: 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. Conclusions: 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. |
topic |
inflammation mkp-5 obesity macrophage adipocytes |
url |
https://www.karger.com/Article/FullText/505343 |
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