PMID- 31962332
OWN - NLM
STAT- MEDLINE
DCOM- 20200923
LR  - 20200923
IS  - 1662-4033 (Electronic)
IS  - 1662-4025 (Print)
IS  - 1662-4025 (Linking)
VI  - 13
IP  - 1
DP  - 2020
TI  - The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity.
PG  - 86-101
LID - 10.1159/000505343 [doi]
AB  - 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.
CI  - (c) 2020 The Author(s) Published by S. Karger AG, Basel.
FAU - Lu, Yuanhua
AU  - Lu Y
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Ma, Jie
AU  - Ma J
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China, 
      ma_jie@jlu.edu.cn.
FAU - Zhao, Jianan
AU  - Zhao J
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Song, Zhuoyao
AU  - Song Z
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Zhou, Chao
AU  - Zhou C
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Liu, Xiu
AU  - Liu X
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Teng, Wenjing
AU  - Teng W
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Wang, Wei
AU  - Wang W
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Yan, Weiqun
AU  - Yan W
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
FAU - Jiao, Ping
AU  - Jiao P
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200121
PL  - Switzerland
TA  - Obes Facts
JT  - Obesity facts
JID - 101469429
RN  - EC 3.1.3.16 (Dusp10 protein, mouse)
RN  - EC 3.1.3.48 (Dual-Specificity Phosphatases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*physiology
MH  - Adipose Tissue/pathology
MH  - Animals
MH  - Cell Communication/*genetics
MH  - Coculture Techniques
MH  - Diet, High-Fat
MH  - Dual-Specificity Phosphatases/genetics/*physiology
MH  - HEK293 Cells
MH  - Humans
MH  - Insulin Resistance/genetics
MH  - Macrophages/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Obesity/etiology/genetics/*pathology
MH  - RAW 264.7 Cells
PMC - PMC7098294
OTO - NOTNLM
OT  - Adipocytes
OT  - Inflammation
OT  - MKP-5
OT  - Macrophage
OT  - Obesity
COIS- The authors declare no potential conflicts of interest.
EDAT- 2020/01/22 06:00
MHDA- 2020/09/24 06:00
PMCR- 2020/01/21
CRDT- 2020/01/22 06:00
PHST- 2019/09/12 00:00 [received]
PHST- 2019/12/08 00:00 [accepted]
PHST- 2020/01/22 06:00 [pubmed]
PHST- 2020/09/24 06:00 [medline]
PHST- 2020/01/22 06:00 [entrez]
PHST- 2020/01/21 00:00 [pmc-release]
AID - 000505343 [pii]
AID - ofa-0013-0086 [pii]
AID - 10.1159/000505343 [doi]
PST - ppublish
SO  - Obes Facts. 2020;13(1):86-101. doi: 10.1159/000505343. Epub 2020 Jan 21.