| Budget Amount *help |
¥38,350,000 (Direct Cost: ¥29,500,000、Indirect Cost: ¥8,850,000)
Fiscal Year 2016: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2015: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Fiscal Year 2014: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
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| Outline of Final Research Achievements |
We have previously shown that increased level of DCA, a secondary bile acid, contributes to liver cancer development in obese mice. However, the precise mechanisms underlying this phenomenon remain unclear. In this study, following findings are obtained: (1) obesity increases the levels of cholesterols and thereby causing production of bile acid. Because high level of bile acid is toxic for many gut bacteria, gut bacteria which are resistant to bile acid, such as secondary bile acid producing bacteria, are preferentially increased in obese mice, resulting in alteration of gut bacterial community in obese mice. (2) Although DCA on its own can provoke senescence-associated secretary phenotype (SASP) in hepatic stellate cells (HSCs) in lean mice, it takes a much longer time as compared to those in obese mice. Here, we show that DCA cooperates with Lipoteichoic acid (LTA), to provoke the onset of SASP in HSCs through toll-like receptor 2 signaling pathway in obese mice.
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