PMID- 22983634
OWN - NLM
STAT- MEDLINE
DCOM- 20130531
LR  - 20211021
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 55
IP  - 12
DP  - 2012 Dec
TI  - Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively 
      activated M2 macrophages and ameliorates insulin resistance and fatty liver in 
      lipoatrophic diabetic A-ZIP transgenic mice.
PG  - 3350-8
LID - 10.1007/s00125-012-2710-2 [doi]
AB  - AIMS/HYPOTHESIS: Monocyte chemoattractant protein-1 (MCP-1)/chemokine (C-C motif) 
      ligand (CCL) 2 (CCL2) secreted from white adipose tissue (WAT) in obesity has 
      been reported to contribute to tissue macrophage accumulation and insulin 
      resistance by inducing a chronic inflammatory state. MCP-1 has been shown to be 
      elevated in the fatty liver of lipoatrophic A-ZIP-transgenic (A-ZIP-Tg) mice. 
      Treatment of these mice with the CC chemokine receptor (CCR) 2 antagonist has 
      been shown to ameliorate the hyperglycaemia, hyperinsulinaemia and hepatomegaly, 
      in conjunction with reducing liver inflammation. However, since CCR2 antagonists 
      can block not only MCP-1 but also MCP-2 (CCL8) and MCP-3 (CCL7), it remains 
      unclear whether MCP-1 secreted from the liver could contribute to hyperglycaemia, 
      hyperinsulinaemia and hepatomegaly in conjunction with liver inflammation, as 
      well as to the M1 and M2 states of macrophage polarisation. METHODS: To address 
      these issues, we analysed the effects of targeted disruption of MCP-1 in A-ZIP-Tg 
      mice. RESULTS: MCP-1 deficiency alone or per se resulted in a significant 
      amelioration of insulin resistance in A-ZIP-Tg mice, which was associated with a 
      suppression of extracellular signal-regulated protein kinase (ERK)-1/2 and p38 
      mitogen-activated protein kinase (p38MAPK) phosphorylation in liver. Although 
      MCP-1 deficiency did not reduce the expression of macrophage markers, it 
      increased the expression of the genes encoding M2 macrophage markers such as Arg1 
      and Chi3l3, as well as significantly reducing the triacylglycerol content of 
      livers from A-ZIP-Tg mice. CONCLUSIONS/ INTERPRETATION: Our data clearly 
      indicated that MCP-1 deficiency improved insulin resistance and hepatic steatosis 
      in A-ZIP-Tg mice and was associated with switching macrophage polarisation and 
      suppressing ERK-1/2 and p38MAPK phosphorylation.
FAU - Nio, Y
AU  - Nio Y
AD  - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
FAU - Yamauchi, T
AU  - Yamauchi T
FAU - Iwabu, M
AU  - Iwabu M
FAU - Okada-Iwabu, M
AU  - Okada-Iwabu M
FAU - Funata, M
AU  - Funata M
FAU - Yamaguchi, M
AU  - Yamaguchi M
FAU - Ueki, K
AU  - Ueki K
FAU - Kadowaki, T
AU  - Kadowaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120916
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tg(AZIP-F)1Vsn protein, mouse)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adipose Tissue, White/*metabolism
MH  - Animals
MH  - Chemokine CCL2/*deficiency
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Diabetes Mellitus, Lipoatrophic/*metabolism
MH  - Fatty Liver/*metabolism
MH  - *Insulin Resistance
MH  - Liver/*metabolism/pathology
MH  - MAP Kinase Signaling System
MH  - Macrophage Activation
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phosphorylation
MH  - Transcription Factors/genetics
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2012/09/18 06:00
MHDA- 2013/06/01 06:00
CRDT- 2012/09/18 06:00
PHST- 2012/05/07 00:00 [received]
PHST- 2012/07/24 00:00 [accepted]
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/06/01 06:00 [medline]
AID - 10.1007/s00125-012-2710-2 [doi]
PST - ppublish
SO  - Diabetologia. 2012 Dec;55(12):3350-8. doi: 10.1007/s00125-012-2710-2. Epub 2012 
      Sep 16.