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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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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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 / ロイコトリエンB4 / インスリン作用 / オミックス解析 |
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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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Report
(4 results)
Research Products
(22 results)
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[Presentation] Adipocyte-specific PDK1 deletion causes insulin resistance, disorder of glucose and lipid metabolism, and NASH2015
Author(s)
Tetsuya Hosooka, Kaku Matsugi, Kazuhiro Nomura, Sho Matsui, Tsutomu Sasaki, Tadahiro Kitamura, Jun Eguchi, Evan D. Rosen, Jun Nakae, Domenico Accili, Masashi Kuroda, Hiroshi Sakaue, Masato Kasuga, and Wataru Ogawa
Organizer
The 8th Asis-Oceania Conference on Obesity
Place of Presentation
Nagoya
Year and Date
2015-10-02
Related Report
Int'l Joint Research
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