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The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity.
Obes Facts 2020; :1-16OF

Abstract

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.

Authors+Show Affiliations

School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China, ma_jie@jlu.edu.cn.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.School of Pharmaceutical Sciences, Jilin University, Changchun, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31962332

Citation

Lu, Yuanhua, et al. "The Role of MKP-5 in Adipocyte-Macrophage Interactions During Obesity." Obesity Facts, 2020, pp. 1-16.
Lu Y, Ma J, Zhao J, et al. The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity. Obes Facts. 2020.
Lu, Y., Ma, J., Zhao, J., Song, Z., Zhou, C., Liu, X., ... Jiao, P. (2020). The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity. Obesity Facts, pp. 1-16. doi:10.1159/000505343.
Lu Y, et al. The Role of MKP-5 in Adipocyte-Macrophage Interactions During Obesity. Obes Facts. 2020 Jan 21;1-16. PubMed PMID: 31962332.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity. AU - Lu,Yuanhua, AU - Ma,Jie, AU - Zhao,Jianan, AU - Song,Zhuoyao, AU - Zhou,Chao, AU - Liu,Xiu, AU - Teng,Wenjing, AU - Wang,Wei, AU - Zhang,Qi, AU - Yan,Weiqun, AU - Jiao,Ping, Y1 - 2020/01/21/ PY - 2019/09/12/received PY - 2019/12/08/accepted PY - 2020/1/22/entrez PY - 2020/1/22/pubmed PY - 2020/1/22/medline KW - Adipocytes KW - Inflammation KW - MKP-5 KW - Macrophage KW - Obesity SP - 1 EP - 16 JF - Obesity facts JO - Obes Facts N2 - 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. SN - 1662-4033 UR - https://www.unboundmedicine.com/medline/citation/31962332/The_Role_of_MKP-5_in_Adipocyte-Macrophage_Interactions_during_Obesity L2 - https://www.karger.com?DOI=10.1159/000505343 DB - PRIME DP - Unbound Medicine ER -