2017 Fiscal Year Final Research Report
Investigation into the molecular mechanism for metabolic disease and NASH using mouse model with adipocyte dysfunction
| Project/Area Number |
15K09389
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | インスリン抵抗性 / 非アルコール性脂肪性肝炎 / 脂肪細胞 / インスリンシグナル / 脂質メディエーター / LTB4 |
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| Outline of Final Research Achievements |
PDK1 is a key molecule which mediates metabolic action of insulin. Adipocyte-specific PDK1 deficient mice develop systemic insulin resistance and nonalcoholic steatohepatitis (NASH). This phenotype in A-PDK1KO mice is suppressed by additional ablation of the transcriptional factor FoxO1 specifically in adipocytes. Taking advantage of lipid mediators metabololipidomics, we uncovered that a lipid mediator LTB4 is involved in the pathogenesis of systemic insulin resistance and NASH. Experiments with isolated adipocytes revealed that insulin inhibits LTB4 production through down-regulation of 5-LO expression via the PDK1-FoxO1 pathway. Thus, 5-LO-LTB4 axis in adipocytes could provide a novel therapeutic target for the treatment of insulin resistance and the related disease.
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| Free Research Field |
代謝学
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