Isolation of physiologically active substance regarding the pathogenesis and development of fatty liver under overeating

• Project/Area Number: 19590779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Oita University
• Principal Investigator: KAKUMA Tetsuya Oita University, 医学部, 助教 (80343359)
• Co-Investigator(Kenkyū-buntansha): YOSHIMATSU Hironobu 大分大学, 医学部, 教授 (00166993) ; SEIKE Masataka 大分大学, 医学部, 助教 (40253794)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 肥満 / 過栄養性脂肪肝 / 炎症性サイトカイン / ヒスタミン / アディポネクチン / pleiotropic効果 / Apelin / 脂肪肝 / チアゾリジン誘導体 / ピオグリタゾン / PPARγ / SREBP / db / dbマウス / KKAyマウス

Research Abstract

脂肪肝に炎症を与えると、脂肪肝の程度は明らかに増悪し致死率が上昇する。その防御システムとしてアディポネクチンやヒスタミンが関与していることが確認された。一部の薬物(降圧薬と高コレステロール治療薬)において過食・高脂肪食による脂肪肝モデルマウスの糖脂質代謝および脂肪肝改善効果が観察された。Apelinという新規物質が高脂肪食負荷肥満モデルマウスの肥満症、過栄養性脂肪肝の治療に効果的であることを実証した。

Research Products

• [Journal Article] Effects of pravastatin on obesity, diabetes, and adiponectin in diet-induced obese mice (2008)
  • Author(s): Araki K, Masaki T, Katsuragi I, Kakuma T, Yoshimatsu H.
  • Journal Title: Obesity (SilverSpring) 16(9) Pages: 2068-2073
  • Peer Reviewed
• [Journal Article] Role of interleukin-6 levels in cardiovascular autonomic dysfunction in type 2 diabetic patients (2008)
  • Author(s): Shinohara T, et al
  • Journal Title: Eur J Nucl Med Mol Imaging 35(9) Pages: 1616-1623
  • Peer Reviewed
• [Journal Article] Initial Japanese Experience with Intragastric Balloon Placement (2008)
  • Author(s): Ohta M, et al
  • Journal Title: Obes Surg July1(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Effects of Pravastatin on Obesity, Diabetes, and Adiponectin in Diet-induced Obese Mice (2008)
  • Author(s): Araki K, et al
  • Journal Title: Obesity (Silver Spring). 16(9) Pages: 2068-2073
  • Peer Reviewed
• [Journal Article] Eetinol binding protein 4 concentrations are influenced by renal function in patients with type 2 diabetes mellitus (2008)
  • Author(s): Masaki T, et al
  • Journal Title: Metabolism 57(10) Pages: 1340-1344
  • Peer Reviewed
• [Journal Article] Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake (2007)
  • Author(s): Gotoh K, Fukagawa K, Fukagawa T, Noguchi H, Kakuma T, Sakata T, Yoshimatsu H.
  • Journal Title: J Neurochem 103(3) Pages: 1102-1110
  • Peer Reviewed
• [Journal Article] TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c) (2007)
  • Author(s): Endo M, Masaki T, Seike M, Yoshimatsu H.
  • Journal Title: Exp Biol Med (Maywood) 232(5) Pages: 614-621
  • Peer Reviewed
• [Journal Article] Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice (2007)
  • Author(s): Higuchi K, Masaki T, Gotoh K, Chiba S, Katsuragi I, Tanaka K, Kakuma T, Yoshimatsu H.
  • Journal Title: Endocrinology 148(6) Pages: 2690-2697
  • Peer Reviewed
• [Journal Article] Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus. (2007)
  • Author(s): Masalii T, et. al.
  • Journal Title: Diabetes Res Clin Pract. 77(2) Pages: 168-173
  • Peer Reviewed
• [Journal Article] Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. (2007)
  • Author(s): Higuchi K, et. al.
  • Journal Title: Endocrinology 148(6) Pages: 2690-2697
  • Peer Reviewed
• [Journal Article] Hypoadiponectinemia in type 2 diabetes mellitus in men is associated with sympathetic overactivity as evaluated by cardiac 123I-metaiodobenzy Iguanidine scintigraphy. (2007)
  • Author(s): Takahashi N, et. al.
  • Journal Title: Metabolism 56(7) Pages: 919-924
  • Peer Reviewed
• [Journal Article] Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake. (2007)
  • Author(s): Gotoh K, et. al.
  • Journal Title: J Neurochem 103(3) Pages: 1102-1110
  • Peer Reviewed
• [Journal Article] Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice (2006)
  • Author(s): Araki K, Masaki T, Katsuragi I, Tanaka K, Kakuma T, Yoshimatsu H.
  • Journal Title: Hypertension 48(1) Pages: 51-57
  • Peer Reviewed
• [Journal Article] Sterol regulatory element binding protein(SREBP)-1 expression in brain is affected by age but not by hormones or metabolic changes (2006)
  • Author(s): Okamoto K, Kakuma T, Fukuchi S, Masaki T, Sakata T, Yoshimatsu H.
  • Journal Title: Brain Res. 1081(1) Pages: 19-27
  • Peer Reviewed
• [Journal Article] The role of histamine H1 receptor and H2 receptor in LPS-induced liver injury (2005)
  • Author(s): Masaki T, Chiba S, Tatsukawa H, Noguchi H, Kakuma T, Endo M, Seike M, Watanabe T, Yoshimatsu H.
  • Journal Title: FASEB J. 19(10) Pages: 1245-1252
  • Peer Reviewed
• [Journal Article] Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice (2004)
  • Author(s): Masaki T, Chiba S, Tatsukawa H, Yasuda T, Noguchi H, Seike M, Yoshimatsu H.
  • Journal Title: Hepatology 40(1) Pages: 177-184
  • Peer Reviewed
• [Presentation] 肥満糖尿病マウスにおいてチアゾリジン誘導体による脂肪肝増悪の機序 (2008)
  • Author(s): 織部淳哉、清家正隆、加隈哲也、原中美環、岡本健二郎、吉松博信
  • Organizer: 第44回日本肝臓学会総会
  • Place of Presentation: 愛媛
• [Presentation] 肥満糖尿病マウスにおいてチアゾリジン誘導体による脂肪肝増悪の機序 (2008)
  • Author(s): 織部淳哉, ほか
  • Organizer: 第44回日本肝臓学会総会
  • Place of Presentation: 松山
• [Presentation] 肥満糖尿病マウスにおけるチアゾリジン誘導体の肝臓、代謝への影響 (2007)
  • Author(s): 織部淳哉、清家正隆、加隈哲也、荒川光江、遠藤美月、吉松博信
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 糖尿病合併脂肪肝症例と非脂肪肝症例の予後の検討 (2007)
  • Author(s): 織部淳哉、清家正隆、針里栄、井上恵、姫野克郎、高橋祐幸、加隈哲也、吉松博信
  • Organizer: 第93回日本消化器病学会総会
  • Place of Presentation: 青森
• [Presentation] 肥満糖尿病マウスにおけるチアゾリジン誘導体の肝臓への影響 (2007)
  • Author(s): 織部淳哉, ほか
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京