2015 Fiscal Year Final Research Report
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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| Keywords | インスリン抵抗性 / 腸管免疫 / 肥満 |
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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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| Free Research Field |
内分泌代謝内科
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