| Project/Area Number |
17K10575
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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 |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
Naitoh Takeshi 東北大学, 医学系研究科, 准教授 (50291258)
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| Co-Investigator(Kenkyū-buntansha) |
井本 博文 東北大学, 大学病院, 助教 (20754922)
田中 直樹 東北大学, 大学病院, 助教 (60547404)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 減量手術 / 十二指腸空腸バイパス術 / 胆汁酸 / 糖尿病 / プロテオーム解析 / 減量・代謝改善手術 / 肥満糖尿病ラット / 代謝改善手術 / 2型糖尿病 / 肥満 |
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| Outline of Final Research Achievements |
Duodenal-jejunal bypass (DJB) shows great effects on host metabolism through bile acid (BA) signaling. However, the mechanism of elevation of serum BA levels after DJB remains unknown. First, we revealed that the enterohepatic circulation of BAs was shortened after DJB. BA levels in the intestine after DJB indicated that BAs would be reabsorbed in the bilio-pancreatic (BP) limb. Second, inhibition study of BA transporters showed that organic-anion transporting peptide played an important role in BA absorption in the BP-limb. BA absorption tended to increase in the absence of lipid solutions compared with that in the presence of lipid solutions. We attributed the increased BA reabsorption in the BP-limb to lack of food in the BP-limb, which contains concentrated BAs and no lipids. Third, proteome analysis suggested that liver carboxylesterase 1d, which is known FXR target gene and improve glucose metabolism through activating PPARα, was involved in the metabolic effects after DJB.
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| Academic Significance and Societal Importance of the Research Achievements |
病的肥満症やそれに伴う糖尿病はしばしば内科治療抵抗性であり、減量手術は現在最も有効な治療方法の一つと考えられている。減量手術後の代謝改善機序の一つとして、血中胆汁酸値の上昇が挙げられているが、詳細な機序は不明であった。本研究は減量手術後に胆汁酸動態が変化する機序や、術後の代謝改善機序の一端を明らかにした。減量手術はまだ発展途上にあり、今回得られた知見は、術式改良に寄与すると考えられるが、それだけでなく、創薬を含め胆汁酸をtargetとした新たな治療法の確立に貢献し得るものと考えられた。
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