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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2006-9-4
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyglucose,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Fabp4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:HashimotoHaruoH,
pubmed-author:IdeTomohiroT,
pubmed-author:KadowakiTakashiT,
pubmed-author:KameiNozomuN,
pubmed-author:KobayashiMasatoshiM,
pubmed-author:KubotaNaotoN,
pubmed-author:KumagaiKatsuyoshiK,
pubmed-author:ManabeIchiroI,
pubmed-author:MurakamiKojiK,
pubmed-author:NagaiRyozoR,
pubmed-author:NishimuraSatoshiS,
pubmed-author:OgataHitomiH,
pubmed-author:OhnishiYasuyukiY,
pubmed-author:OhsugiMitsuruM,
pubmed-author:Ohtsuka-KowatariNorieN,
pubmed-author:OishiYumikoY,
pubmed-author:SakamotoKentaroK,
pubmed-author:SuzukiRyoR,
pubmed-author:TobeKazuyukiK,
pubmed-author:TokuyamaKumpeiK,
pubmed-author:TsunodaMasakiM,
pubmed-author:UekiKohjiroK,
pubmed-author:WatanabeTakuT,
pubmed-author:YamauchiToshimasaT
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26602-14
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16809344-Adipose Tissue,
pubmed-meshheading:16809344-Animals,
pubmed-meshheading:16809344-Antimetabolites,
pubmed-meshheading:16809344-Body Weight,
pubmed-meshheading:16809344-Cells, Cultured,
pubmed-meshheading:16809344-Chemokine CCL2,
pubmed-meshheading:16809344-Deoxyglucose,
pubmed-meshheading:16809344-Diet,
pubmed-meshheading:16809344-Dietary Fats,
pubmed-meshheading:16809344-Fatty Acid-Binding Proteins,
pubmed-meshheading:16809344-Fatty Acids, Nonesterified,
pubmed-meshheading:16809344-Glucose,
pubmed-meshheading:16809344-Glucose Clamp Technique,
pubmed-meshheading:16809344-Insulin,
pubmed-meshheading:16809344-Insulin Resistance,
pubmed-meshheading:16809344-Interleukin-6,
pubmed-meshheading:16809344-Macrophages,
pubmed-meshheading:16809344-Mice,
pubmed-meshheading:16809344-Mice, Inbred C57BL,
pubmed-meshheading:16809344-Mice, Obese,
pubmed-meshheading:16809344-Mice, Transgenic,
pubmed-meshheading:16809344-Myoblasts, Skeletal,
pubmed-meshheading:16809344-Promoter Regions, Genetic,
pubmed-meshheading:16809344-Signal Transduction,
pubmed-meshheading:16809344-Tumor Necrosis Factor-alpha
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pubmed:year |
2006
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pubmed:articleTitle |
Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance.
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pubmed:affiliation |
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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