Physiological roles of intestinal macrophage Foxo1 in HFD-induced insulin resistance
| Project/Area Number |
26860338
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | インスリン抵抗性 / 腸管免疫 / 肥満 / 慢性炎症 / 高脂肪食 / Foxo1 / マクロファージ |
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| Outline of Final Research Achievements |
To investigate the pathophysiological role of colonic macrophage, We generated intestinal epithelial cell-specific tamoxifen inducible Ccl2 knockout mice (Vil-Ccl2KO) , Macrophage specific Ccr2 knockout mice(M-Ccr2KO)and Macrophage specific PDK1 knockout mice(Foxo1 activation model). Foxo1 in macrophage directly induced Ccr2 expression(Kawano Y. et al, Diabetes. 2012) Vil-Ccl2KO and M-Ccr2KO exhibit significantly improved glucose tolerance and insulin sensitivity compared to control mice under 12-week-HFD. Deletion of Ccl2 in intestinal epithelial cell reduced infiltration of colonic macrophage, leading to amelioration of HFD-induced intestinal barrier dysfunction, endotoxemia and chronic inflammation in adipose tissue. These data indicate that inhibition pro-inflammatory macrophages infiltration in colon prevents from HFD-induced insulin resistance.
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Report
(3 results)
Research Products
(9 results)
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[Presentation] Colonic Proinflammatory Macrophage-Ccl2 Axis Regulates Metabolic Homeostasis through IL18 from Inflammasome2016
Author(s)
○Kawano Y, Watanabe N, Kikuchi T, Tateya S, Tamori Y, Kaneko M, Abe T, Onodera M, Nakae J, Itoh H.
Organizer
Ameriacan Diabetes Association, NEW ORLEANS
Place of Presentation
NEW ORLEANS(USA)
Year and Date
2016-06-12
Related Report
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