PMID- 20056828
OWN - NLM
STAT- MEDLINE
DCOM- 20100326
LR  - 20100222
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 151
IP  - 3
DP  - 2010 Mar
TI  - An increase in the circulating concentration of monocyte chemoattractant 
      protein-1 elicits systemic insulin resistance irrespective of adipose tissue 
      inflammation in mice.
PG  - 971-9
LID - 10.1210/en.2009-0926 [doi]
AB  - Chronic inflammation in adipose tissue is thought to be important for the 
      development of insulin resistance in obesity. Furthermore, the level of monocyte 
      chemoattractant protein-1 (MCP-1) is increased not only in adipose tissue but 
      also in the circulation in association with obesity. However, it has remained 
      unclear to what extent the increased circulating level of MCP-1 contributes to 
      insulin resistance. We have now examined the relevance of circulating MCP-1 to 
      the development of insulin resistance in mice. The plasma concentration of MCP-1 
      was increased chronically or acutely in mice to the level observed in obese 
      animals by chronic subcutaneous infusion of recombinant MCP-1 with an osmotic 
      pump or by acute intravenous infusion of MCP-1 with an infusion pump, 
      respectively. Whole-body metabolic parameters as well as inflammatory changes in 
      adipose tissue were examined. A chronic increase in the circulating level of 
      MCP-1 induced insulin resistance, macrophage infiltration into adipose tissue, 
      and an increase in hepatic triacylglycerol content. An acute increase in the 
      circulating MCP-1 concentration also induced insulin resistance but not 
      macrophage infiltration into adipose tissue. In addition, inhibition of signaling 
      by MCP-1 and its receptor CCR2 by administration of a novel CCR2 antagonist 
      ameliorated insulin resistance in mice fed a high-fat diet without affecting 
      macrophage infiltration into adipose tissue. These data indicate that an increase 
      in the concentration of MCP-1 in the circulation is sufficient to induce systemic 
      insulin resistance irrespective of adipose tissue inflammation.
FAU - Tateya, Sanshiro
AU  - Tateya S
AD  - Division of Diabetes, Metabolism, and Endocrinology, Department of Internal 
      Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
FAU - Tamori, Yoshikazu
AU  - Tamori Y
FAU - Kawaguchi, Takayuki
AU  - Kawaguchi T
FAU - Kanda, Hajime
AU  - Kanda H
FAU - Kasuga, Masato
AU  - Kasuga M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100107
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dietary Fats)
RN  - 0 (Receptors, CCR2)
SB  - IM
MH  - Adipose Tissue/immunology
MH  - Animals
MH  - Chemokine CCL2/administration & dosage/*blood
MH  - Dietary Fats/adverse effects
MH  - Fatty Liver/etiology
MH  - *Insulin Resistance
MH  - Macrophages/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/complications/immunology/*metabolism
MH  - Receptors, CCR2/antagonists & inhibitors/*metabolism
MH  - Signal Transduction
EDAT- 2010/01/09 06:00
MHDA- 2010/03/27 06:00
CRDT- 2010/01/09 06:00
PHST- 2010/01/09 06:00 [entrez]
PHST- 2010/01/09 06:00 [pubmed]
PHST- 2010/03/27 06:00 [medline]
AID - en.2009-0926 [pii]
AID - 10.1210/en.2009-0926 [doi]
PST - ppublish
SO  - Endocrinology. 2010 Mar;151(3):971-9. doi: 10.1210/en.2009-0926. Epub 2010 Jan 7.