PMID- 16691291
OWN - NLM
STAT- MEDLINE
DCOM- 20060801
LR  - 20220408
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 116
IP  - 6
DP  - 2006 Jun
TI  - MCP-1 contributes to macrophage infiltration into adipose tissue, insulin 
      resistance, and hepatic steatosis in obesity.
PG  - 1494-505
AB  - Adipocytes secrete a variety of bioactive molecules that affect the insulin 
      sensitivity of other tissues. We now show that the abundance of monocyte 
      chemoattractant protein-1 (MCP-1) mRNA in adipose tissue and the plasma 
      concentration of MCP-1 were increased both in genetically obese diabetic (db/db) 
      mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to 
      express an MCP-1 transgene in adipose tissue under the control of the aP2 gene 
      promoter exhibited insulin resistance, macrophage infiltration into adipose 
      tissue, and increased hepatic triglyceride content. Furthermore, insulin 
      resistance, hepatic steatosis, and macrophage accumulation in adipose tissue 
      induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice 
      compared with WT animals. Finally, acute expression of a dominant-negative mutant 
      of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a 
      high-fat diet. These findings suggest that an increase in MCP-1 expression in 
      adipose tissue contributes to the macrophage infiltration into this tissue, 
      insulin resistance, and hepatic steatosis associated with obesity in mice.
FAU - Kanda, Hajime
AU  - Kanda H
AD  - Department of Clinical Molecular Medicine, Kobe University Graduate School of 
      Medicine, Kobe, Japan.
FAU - Tateya, Sanshiro
AU  - Tateya S
FAU - Tamori, Yoshikazu
AU  - Tamori Y
FAU - Kotani, Ko
AU  - Kotani K
FAU - Hiasa, Ken-ichi
AU  - Hiasa K
FAU - Kitazawa, Riko
AU  - Kitazawa R
FAU - Kitazawa, Sohei
AU  - Kitazawa S
FAU - Miyachi, Hitoshi
AU  - Miyachi H
FAU - Maeda, Sakan
AU  - Maeda S
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Kasuga, Masato
AU  - Kasuga M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060511
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dietary Fats)
RN  - 0 (RNA, Messenger)
RN  - 0 (Triglycerides)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3 Cells
MH  - Adipose Tissue/cytology/*metabolism
MH  - Animals
MH  - Chemokine CCL2/*blood/genetics
MH  - Dietary Fats
MH  - *Fatty Liver
MH  - Glucose/metabolism
MH  - Humans
MH  - *Insulin Resistance
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - Mice, Transgenic
MH  - Obesity/*physiopathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/metabolism
MH  - Triglycerides/metabolism
PMC - PMC1459069
EDAT- 2006/05/13 09:00
MHDA- 2006/08/02 09:00
PMCR- 2006/06/01
CRDT- 2006/05/13 09:00
PHST- 2005/08/04 00:00 [received]
PHST- 2006/03/14 00:00 [accepted]
PHST- 2006/05/13 09:00 [pubmed]
PHST- 2006/08/02 09:00 [medline]
PHST- 2006/05/13 09:00 [entrez]
PHST- 2006/06/01 00:00 [pmc-release]
AID - 26498 [pii]
AID - 10.1172/JCI26498 [doi]
PST - ppublish
SO  - J Clin Invest. 2006 Jun;116(6):1494-505. doi: 10.1172/JCI26498. Epub 2006 May 11.