Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Outline of Final Research Achievements |
The physiological function of ABC transporters in liver bile canaliculi is regulated by canalicular translocation and/or internalization into cytosol, we investigated how hypernutirition and/or pathological condition cause the dysfunction of canalicular trafficking of ABC transporters. As a result, we found that protein kinase A is involved in the canalicular localization of cholesterol transporter Abcg5/Abcg8 induced by high-fat diet consumption. Furthermore, we found that the concentration of bile acids decreased in high-fat diet fed mice. This event was thought to be involved in the mislocalization of bile acids transporter Abcb11 via conventional protein kinase C signaling. These results suggest that the high-fat diet perturbed the distribution of ABC transporters in hepatocytes, which led to the supersaturation and crystallization of cholesterol in bile.
|