Role of ileal bile acid absorption on regulation of serum cholesterol levels

• Project/Area Number: 20590137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: MIYATA Masaaki Tohoku University, 大学院・薬学研究科, 助教 (90239418)
• Co-Investigator(Kenkyū-buntansha): YOSHINARI Kouichi 東北大学, 大学院・薬学研究科, 准教授 (60343399)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ASBT / コレステロール / 胆汁酸 / FXR / 腸内細菌 / 抗菌薬 / 回腸胆汁酸吸収 / 二次胆汁酸 / アンピシリン / 消化管吸収 / 発現調節

Research Abstract

Intestinal bile acid absorption is negatively regulated through cholesterol signaling in an FXR-independent manner. Intestinal bile acid absorption is also regulated through enterobacteria-mediated bile acid transformation.

Research Products

• [Journal Article] Enterobacteria modulate intestinal bile acid transport and homeostasis through apical sodium-dependent bile acid transporter (SLC10A2) expression (2011)
  • Author(s): M.Miyata, H.Yamakawa, M.Hamatsu, H.Kuribayashi, Y.Takamatsu, Y.Yamazoe
  • Journal Title: J.Pharmacol.Exp.Ther. 336 Pages: 188-196
  • Peer Reviewed
• [Journal Article] Enterobacteria modulate intestinal bile acid transport and homeostasis through apical sodium-dependent bile acid transporter (SLC10A2) expression (2011)
  • Author(s): M.Miyata, et al.
  • Journal Title: J.Pharmacol.Exp.Ther. Volume: 336 Pages: 188-196
  • Peer Reviewed
• [Journal Article] Possible protective-role of pregnenolone-16α-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis. (2010)
  • Author(s): M.Miyata, M.Nomoto, F.Sotodate, T.Mizuki, W.Hori, M.Nagayasu, S.Yokokawa, S.Ninomiya, Y.Yamazoe.
  • Journal Title: Eur.J.Pharmacol. 636 Pages: 145-154
  • Peer Reviewed
• [Journal Article] Possible protcctive-role of pregnenolone-16α-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis. (2010)
  • Author(s): M.Miyata, et al.
  • Journal Title: Eur.J.Pharmacol Volume: 636 Pages: 145-154
  • Peer Reviewed
• [Journal Article] Administration of ampicillin elevates hepatic primary bile acid synthesis through suppression of ileal FGF15 expression (2009)
  • Author(s): M.Miyata, Y.Takamatsu, H.Kuribayashi, Y.Yamazoe.
  • Journal Title: J.Pharmacol.Exp.Ther. 331 Pages: 1079-1085
  • Peer Reviewed
• [Journal Article] Cholesterol feeding prevents hepatic accumulation of bile acids in cholic acid-fed Fxr-null mice : FXR-independent suppression of intestinal bile acid absorption (2009)
  • Author(s): M.Miyata, Y.Matsuda, M.Nomoto, Y.Takamatsu, N.Sato, M.Hamatsu, P.A.Dawson, F.J.Gonzalez, Y.Yamazoe.
  • Journal Title: Drug Metab.Dispos. 37 Pages: 338-344
  • Peer Reviewed
• [Journal Article] Administration of ampicillin elevates hepatic primary bile acid synthesis through suppression of ileal FGF15 expression (2009)
  • Author(s): M.Miyata, et al.
  • Journal Title: J.Pharmacol.Exp.Ther. 331 Pages: 1079-1085
  • Peer Reviewed
• [Journal Article] Cholesterol feeding prevents hepatic accumulation of bile acids in cholic acid-fed Fxr-null mice : FXR-independent suppression of intestinal bile acid absorption (2009)
  • Author(s): M. Miyata, et.al.
  • Journal Title: Drug Metab. Dispos. 37 Pages: 338-344
  • Peer Reviewed
• [Journal Article] PPARa gene expression is up-regulated by LXR and PXR activators in the small intestine. (2008)
  • Author(s): J.Inoue, S.Satoh, M.Kita, M.Nakahara, S.Hachimura, M.Miyata, T.Nishimaki-Mogami, R.Sato
  • Journal Title: Biochem.Biophys.Res.Commun. 371 Pages: 675-678
  • Peer Reviewed
• [Journal Article] PPARa gene expression is up-regulated by LXR and PXR activators in the small intestine (2008)
  • Author(s): J. Inoue, et.al.
  • Journal Title: Biochem. Biophys. Res. Commun. 371 Pages: 675-678
  • Peer Reviewed
• [Presentation] 胆汁酸代謝を介する腸内細菌による回腸エンドクラインホルモンFGF15の発現調節 (2011)
  • Author(s): 宮田昌明, 他3名
  • Organizer: 第131回日本薬学会年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-30
• [Presentation] 腸内細菌は胆汁酸代謝を介した回腸ASBT発現抑制により宿主の胆汁酸吸収を制御する (2010)
  • Author(s): 山川泰輝、栗林秀明、宮田昌明、山添康
  • Organizer: 第32回胆汁酸研究会
  • Place of Presentation: 仙台
  • Year and Date: 2010-11-06
• [Presentation] 抗菌薬投与は胆汁酸トランスポーター、合成酵素の発現亢進を介して胆汁酸ホメオスタシスを変動させる (2010)
  • Author(s): 宮田昌明、山川泰輝、栗林秀明、濱津真由美、高松裕樹、山添康
  • Organizer: 第25回日本薬物動態学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-09
• [Presentation] 腸内細菌は回腸ASBT 発現を介して消化管の胆汁酸吸収を調節する (2010)
  • Author(s): 山川泰輝、宮田昌明、栗林秀明、高松裕樹、濱津真由美、山添康
  • Organizer: 第25回日本薬物動態学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-07
• [Presentation] 腸内細菌は回腸ASBT発現を介して消化管の胆汁酸吸収を調節する (2010)
  • Author(s): 山川泰輝, 他5名
  • Organizer: 第25回日本薬物動態学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-07
• [Presentation] 抗菌薬による腸内細菌叢の変動は回腸胆汁酸吸収トランスポーターASBTの発現上昇に関与する (2010)
  • Author(s): 宮田昌明、山川泰輝、栗林秀明、濱津真由美、山添康
  • Organizer: 第37回日本トキシコロジー学会年会
  • Place of Presentation: 宜野湾
  • Year and Date: 2010-06-17
• [Presentation] Enterobacteria alter bile acid homeostasis through FXR-FGF15/19 system (2010)
  • Author(s): 山添康, 高松裕樹, 栗林秀明, 山川泰輝, 宮田昌明
  • Organizer: Microsomal Drug Oxidation
  • Place of Presentation: Beijin, Chaina
  • Year and Date: 2010-05-18
• [Presentation] Administration of ampicillin increases ileal Asbt protein amounts resulting in reduction of fecal bile acid excretion in mice. (2010)
  • Author(s): 山添康, 高松裕樹, 濱津真由美, 宮田昌明
  • Organizer: 2010 Experimental Biology
  • Place of Presentation: Anaheim USA
  • Year and Date: 2010-04-27
• [Presentation] Administration of ampicillin elevates hepatic primary bile acid synthesis through suppression of ileal FGF 15 expression. (2010)
  • Author(s): Masaaki Miyata, 他3名
  • Organizer: 2010 Experlmental Biology
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2010-04-26
• [Presentation] Administration of ampicillin increases ileal Asbt protein amounts resulting in reduction of fecal bile acid exeretion in mice. (2010)
  • Author(s): Yasushi Yamazoe, 他4名
  • Organizer: 2010 Experimental Biology
  • Place of Presentation: Anaheim USA
  • Year and Date: 2010-04-26
• [Presentation] アンピシリン投与はマウス回腸の胆汁酸吸収トランスポータータンパク含量を増加させ、糞中胆汁酸排泄を低下させる (2010)
  • Author(s): 宮田昌明、山川泰輝、濱津真由美、高松裕樹、山添康
  • Organizer: 日本薬学会第130回年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 抗菌薬の投与は回腸FGF15の発現低下を介して一次胆汁酸合成を増加させる (2009)
  • Author(s): 宮田昌明, 他3名
  • Organizer: 第24回 日本薬物動態学会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-27
• [Presentation] 消化管FGF15の発現変動と胆汁酸組成 (2009)
  • Author(s): 宮田昌明, 他4名
  • Organizer: 第31回胆汁酸研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-07
• [Presentation] アンピシリン投与による肝内胆汁酸濃度上昇における消化管と肝臓の寄与 (2009)
  • Author(s): 濱津真由美、高松裕樹、宮田昌明、山添康
  • Organizer: 第48回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-18
• [Presentation] 腸内細菌ーFGF系による肝胆汁酸レベルの調節 (2009)
  • Author(s): 宮田昌明、高松裕樹、山添康
  • Organizer: 第36回日本トキシコロジー学会年会
  • Place of Presentation: 盛岡
  • Year and Date: 2009-07-08
• [Presentation] 腸内細菌-FGF系による肝胆汁酸レベルの調節 (2009)
  • Author(s): 宮田昌明, 他2名
  • Organizer: 第36回日本トキシコロジー学会年会
  • Place of Presentation: 盛岡
  • Year and Date: 2009-07-08
• [Presentation] 脂質とFXR control (2008)
  • Author(s): 宮田昌明(他3名)
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-30
• [Presentation] 抗生物質投与による肝内胆汁酸濃度上昇とその機序 (2008)
  • Author(s): 高松裕樹、宮田昌明,山添康
  • Organizer: 第47回日本薬学会東北支部会
  • Place of Presentation: 盛岡
  • Year and Date: 2008-10-26
• [Presentation] 抗菌薬投与による肝内胆汁酸濃度の上昇と回腸FGF15の発現抑制 (2008)
  • Author(s): 宮田昌明(他2名)
  • Organizer: 第30回胆汁酸研究会
  • Place of Presentation: 広島
  • Year and Date: 2008-10-18
• [Presentation] 核内受容体FXRの欠損は、肝内胆汁酸濃度の上昇を引き起こし、酸化ストレスの生成を促進する (2008)
  • Author(s): 宮田昌明(他2名)
  • Organizer: 第5回東日本胆汁酸研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-19
• [Presentation] アンピシリン併用により生ずるコール酸誘発肝障害と胆汁酸動態 (2008)
  • Author(s): 高松裕樹、宮田昌明、山添康
  • Organizer: 第35回日本トキシコロジー学会学術年会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-26
• [Presentation] コレステロールによる肝内胆汁酸レベルの調節機序の解明-Fxr欠損マウスによる解析 (2008)
  • Author(s): 佐藤望未(他5名)
  • Organizer: 日本薬学会第128回年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-26
• [Remarks] ホームページ等