| 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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| 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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