PMID- 16809344
OWN - NLM
STAT- MEDLINE
DCOM- 20061218
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 36
DP  - 2006 Sep 8
TI  - Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes 
      macrophage recruitment and insulin resistance.
PG  - 26602-14
AB  - Adipose tissue expression and circulating concentrations of monocyte 
      chemoattractant protein-1 (MCP-1) correlate positively with adiposity. To 
      ascertain the roles of MCP-1 overexpression in adipose, we generated transgenic 
      mice by utilizing the adipocyte P2 (aP2) promoter (aP2-MCP-1 mice). These mice 
      had higher plasma MCP-1 concentrations and increased macrophage accumulation in 
      adipose tissues, as confirmed by immunochemical, flow cytometric, and gene 
      expression analyses. Tumor necrosis factor-alpha and interleukin-6 mRNA levels in 
      white adipose tissue and plasma non-esterified fatty acid levels were increased 
      in transgenic mice. aP2-MCP-1 mice showed insulin resistance, suggesting that 
      inflammatory changes in adipose tissues may be involved in the development of 
      insulin resistance. Insulin resistance in aP2-MCP-1 mice was confirmed by 
      hyperinsulinemic euglycemic clamp studies showing that transgenic mice had lower 
      rates of glucose disappearance and higher endogenous glucose production than 
      wild-type mice. Consistent with this, insulin-induced phosphorylations of Akt 
      were significantly decreased in both skeletal muscles and livers of aP2-MCP-1 
      mice. MCP-1 pretreatment of isolated skeletal muscle blunted insulin-stimulated 
      glucose uptake, which was partially restored by treatment with the MEK inhibitor 
      U0126, suggesting that circulating MCP-1 may contribute to insulin resistance in 
      aP2-MCP-1 mice. We concluded that both paracrine and endocrine effects of MCP-1 
      may contribute to the development of insulin resistance in aP2-MCP-1 mice.
FAU - Kamei, Nozomu
AU  - Kamei N
AD  - Department of Metabolic Diseases, Graduate School of Medicine, University of 
      Tokyo, Tokyo 113-8655, Japan.
FAU - Tobe, Kazuyuki
AU  - Tobe K
FAU - Suzuki, Ryo
AU  - Suzuki R
FAU - Ohsugi, Mitsuru
AU  - Ohsugi M
FAU - Watanabe, Taku
AU  - Watanabe T
FAU - Kubota, Naoto
AU  - Kubota N
FAU - Ohtsuka-Kowatari, Norie
AU  - Ohtsuka-Kowatari N
FAU - Kumagai, Katsuyoshi
AU  - Kumagai K
FAU - Sakamoto, Kentaro
AU  - Sakamoto K
FAU - Kobayashi, Masatoshi
AU  - Kobayashi M
FAU - Yamauchi, Toshimasa
AU  - Yamauchi T
FAU - Ueki, Kohjiro
AU  - Ueki K
FAU - Oishi, Yumiko
AU  - Oishi Y
FAU - Nishimura, Satoshi
AU  - Nishimura S
FAU - Manabe, Ichiro
AU  - Manabe I
FAU - Hashimoto, Haruo
AU  - Hashimoto H
FAU - Ohnishi, Yasuyuki
AU  - Ohnishi Y
FAU - Ogata, Hitomi
AU  - Ogata H
FAU - Tokuyama, Kumpei
AU  - Tokuyama K
FAU - Tsunoda, Masaki
AU  - Tsunoda M
FAU - Ide, Tomohiro
AU  - Ide T
FAU - Murakami, Koji
AU  - Murakami K
FAU - Nagai, Ryozo
AU  - Nagai R
FAU - Kadowaki, Takashi
AU  - Kadowaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060629
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antimetabolites)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dietary Fats)
RN  - 0 (Fabp4 protein, mouse)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue/cytology/*metabolism
MH  - Animals
MH  - Antimetabolites/metabolism
MH  - Body Weight
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Deoxyglucose/metabolism
MH  - Diet
MH  - Dietary Fats
MH  - Fatty Acid-Binding Proteins/genetics/metabolism
MH  - Fatty Acids, Nonesterified/metabolism
MH  - Glucose/metabolism
MH  - Glucose Clamp Technique
MH  - Insulin/metabolism
MH  - Insulin Resistance/*immunology
MH  - Interleukin-6/genetics/metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Mice, Transgenic
MH  - Myoblasts, Skeletal/cytology/metabolism
MH  - Promoter Regions, Genetic
MH  - Signal Transduction/physiology
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2006/07/01 09:00
MHDA- 2006/12/19 09:00
CRDT- 2006/07/01 09:00
PHST- 2006/07/01 09:00 [pubmed]
PHST- 2006/12/19 09:00 [medline]
PHST- 2006/07/01 09:00 [entrez]
AID - S0021-9258(19)35191-9 [pii]
AID - 10.1074/jbc.M601284200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Sep 8;281(36):26602-14. doi: 10.1074/jbc.M601284200. Epub 2006 
      Jun 29.