2011 Fiscal Year Final Research Report
Role of CCR5 and CX3CR1 in the development of insulin resistance
| Project/Area Number |
22790854
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Metabolomics
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| Research Institution | Kanazawa University |
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Principal Investigator |
OTA Tsuguhito 金沢大学, フロンティアサイエンス機構, 特任助教 (60397213)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 炎症 / インスリン抵抗性 / ケモカイン / 脂肪組織 / 肥満 / マクロファージ |
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| Research Abstract |
Monocyte chemoattractant protein-1(MCP-1) and its receptor CCR2 are pivotal for adipose tissue macrophage(ATM) recruitment and the development of insulin resistance. However, other chemokine systems may also play a role in these processes. In this study, we investigated the role of CCR5 in obesity-induced adipose tissue inflammation and insulin resistance. We analyzed expression levels of CCR5 and its ligands in white adipose tissue(WAT) of genetically(ob/ob) and high-fat(HF) diet-induced obese(DIO) mice. CCR5 and its ligands were markedly upregulated in WAT of DIO and ob/ob mice. Fluorescence-activated cell sorter analysis also revealed that DIO mice had a robust increase in CCR5+cells within ATMs compared with chow-fed mice. Furthermore, Ccr5-/-mice were protected from insulin resistance, glucose intolerance, and hepatic steatosis induced by HF feeding. The effects of loss of CCR5 were related to both reduction of total ATM content and an M2 dominant shift in ATM polarization. Thus, CCR5 plays a critical role in ATM recruitment and polarization and subsequent development of insulin resistance.
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Research Products
(30 results)
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[Journal Article] Endoplasmic reticulum stress inhibits STAT3-dependent suppression of hepatic gluconeogenesis via dephosphorylation and deacetylation2012
Author(s)
Kimura K, Yamada T, Matsumoto M, Kido Y, Hosooka T, Asahara S, Matsuda T, Ota T, Watanabe H, Sai Y, Miyamoto K, Kaneko S, Kasuga M, Inoue H
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Journal Title
Diabetes
Volume: 61
Pages: 61-73
Peer Reviewed
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[Journal Article] A liver-derived secretory protein, selenoprotein P, causes insulin resistance2010
Author(s)
Misu H, Takamura T, Takayama H, Hayashi H, Matsuzawa-Nagata N, Kurita S, Ishikura K, Ando H, Takeshita Y, Ota T, Sakurai M, Yamashita T, Mizukoshi E, Honda M, Miyamoto K, Kubota T, Kubota N, Kadowaki T, Kim HJ, Lee IK, Minokoshi Y, Saito Y, Takahashi K, Yamada Y, Takakura N, Kaneko S
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Journal Title
Cell Metab
Volume: 12
Pages: 483-495
Peer Reviewed
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[Journal Article] Effect of pioglitazone on muscle sympathetic nerve activity in type 2 diabetes mellitus with alpha-glucosidase inhibitor2010
Author(s)
Kobayashi D, Takamura M, Murai H, Usui S, Ikeda T, Inomata J, Takashima S, Kato T, Furusho H, Takeshita Y, Ota T, Takamura T, Kaneko S
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Journal Title
Auton Neurosci
Volume: 158
Pages: 86-91
Peer Reviewed
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[Journal Article] CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status
Author(s)
Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, Takamura T, Yamamoto H, Miyamoto K, Ginsberg HN, Mukaida N, Kaneko S, Ota T
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Journal Title
DOI
Peer Reviewed
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[Presentation] 肥満によるる脂肪組織マクロファージの量の変化と質の調節が関わるインスリン抵抗性の発症にはCCR5によ2011
Author(s)
澤本一樹,北出紘規, Ni Yinhua,山本靖彦,井上啓,篁俊成,宮本謙一,山本博,向田直史,金子周一,太田嗣人
Organizer
第54回日本糖尿病学会年次学術集会
Place of Presentation
ロイトン札幌(北海道)
Year and Date
2011-05-21
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