Adipocytokines and cardio-renal diseases

• Project/Area Number: 23790845
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagoya University
• Principal Investigator: SHIBATA Rei 名古屋大学, 医学(系)研究科(研究院), 特任講師 (70343689)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 脂肪細胞由来因子 / アディポネクチン / 心不全 / 腎不全 / サイトカイン / 敗血症 / アディポサイトカイン / 慢性腎臓病

Research Abstract

Adipose tissue functions as an endocrine organ by secreting adipocytokines that can directly affect nearby or remote organs. Adiponectin is an adipocytokine whose concentration is down-regulated in subjects with obesity-related disorders. Low levels of circulating adiponectin appear to associate with the increased prevalence of obesity-linked diseases including cardiac and renal dysfunction. In our study, we have shown that adiponectin exerts beneficial effects on the cardio-renal system by directly acting on the component cells in the heart and kidney. The cardiovascular protection by adiponectin is mediated through its ability to attenuate apoptotic activity in the target organs. Thus, adiponectin could represent a therapeutic target molecule for prevention or treatment of cardio-renal diseases.

Research Products

• [Journal Article] Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation (2013)
  • Author(s): Uemura Y, Shibata R, Ohashi K, Enomoto T,Kambara T, Yamamoto T, Ogura Y, Yuasa D,Joki Y, Matsuo K, Miyabe M, Kataoka Y,Murohara T and Ouchi N
  • Journal Title: FASEB journal Volume: 27 Pages: 25-33
  • Peer Reviewed
• [Journal Article] Adiponectin-mediated modulation of lymphatic vessel formation and lymphedema (2013)
  • Author(s): Shimizu Y, Shibata R, Ishii M, Ohashi K,Kambara T, Uemura Y, Yuasa D, Kataoka Y,Kihara S, Murohara T and Ouchi N
  • Journal Title: Journal of the American Heart Association Volume: 2
  • Peer Reviewed
• [Journal Article] Adiponectin-mediated modulation of lymphatic vessel formation and lymphedema (2013)
  • Author(s): Shimizu Y, Shibata R, Ishii M, Ohashi K, Kambara T, Uemura Y, Yuasa D, Kataoka Y, Kihara S, Murohara T, Ouchi N
  • Journal Title: J Am Heart Assoc Volume: 2 Issue: 5
  • DOI: 10.1161/jaha.113.000438
  • Peer Reviewed
• [Journal Article] Impact of adiponectin and leptin on long-term adverse events in japanese patients with acute myocardial infarction. (2013)
  • Author(s): Morita Y, Maeda K, Kondo T, Ishii H, Matsudaira K, Okumura N, Mitsuhashi H, Shibata R, Murohara T.
  • Journal Title: Circ J. Volume: 77 Pages: 2778-2785
  • Peer Reviewed
• [Journal Article] Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation (2013)
  • Author(s): Uemura Y, Shibata R, Ohashi K, Enomoto T, Kambara T, Yamamoto T, Ogura Y, Yuasa D, Joki Y, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N
  • Journal Title: FASEB J Volume: 27 Issue: 1 Pages: 25-33
  • DOI: 10.1096/fj.12-213744
  • Peer Reviewed
• [Journal Article] iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis. (2013)
  • Author(s): Kito T, Shibata R, Ishii M, Suzuki H, Himeno T, Kataoka Y, Yamamura Y, Yamamoto T, Nishio N, Ito S, Numaguchi Y, Tanigawa T, Yamashita JK, Ouchi N, Honda H, Isobe K, Murohara T.
  • Journal Title: Sci Rep Volume: 11:3 Issue: 1 Pages: 1418-1418
  • DOI: 10.1038/srep01418
  • Peer Reviewed
• [Journal Article] Therapeutic Reendothelialization by Induced Pluripotent Stem Cells After Vascular Injury (2013)
  • Author(s): Yamamoto T, Shibata R, Ishii M, Kanemura N, Kito T, Suzuki H, Miyake H, Maeda K, Tanigawa T, Ouchi N, Murohara T
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 33 Issue: 9 Pages: 2218-21
  • DOI: 10.1161/atvbaha.113.301313
  • Peer Reviewed
• [Journal Article] iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis (2013)
  • Author(s): Kito T, Shibata R, Ishii M, Suzuki H, Himeno T, Kataoka Y, Yamamura Y, Yamamoto T, Nishio N, Ito S, Numaguchi Y, Tanigawa T, Yamashita JK, Ouchi N, Honda H, Isobe K, Murohara T
  • Journal Title: Sci Rep Volume: in press
  • Peer Reviewed
• [Journal Article] Circulating cathepsin k as a potential novel biomarker of coronary artery disease. (2013)
  • Author(s): Cheng XW, Kikuchi R, Ishii H, Yoshikawa D, Hu L, Takahashi R, Shibata R, Ikeda N, Kuzuya M, Okumura K, Murohara T.
  • Journal Title: Atherosclerosis. Volume: in press
  • Peer Reviewed
• [Journal Article] Protective role of adiponectin in cardiovascular disease (2012)
  • Author(s): Shibata R, Murohara T and Ouchi N
  • Journal Title: Current medicinal chemistry Volume: 19 Pages: 5459-66
  • Peer Reviewed
• [Journal Article] Therapeutic impact offollistatin-like 1 on myocardial ischemic injury in preclinical models (2012)
  • Author(s): Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S,Yuasa D, Matsuo K, Enomoto T, Uemura Y,Miyabe M, Ishii M, Yamamoto T, Shimizu Y,Walsh K and Murohara T
  • Journal Title: Circulation Volume: 126 Pages: 1728-38
  • Peer Reviewed
• [Journal Article] Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism (2012)
  • Author(s): Maruyama S, Shibata R, Kikuchi R, Izumiya Y,Rokutanda T, Araki S, Kataoka Y, Ohashi K,Daida H, Kihara S, Ogawa H, Murohara T and Ouchi N
  • Journal Title: The Journal of biological chemistry Volume: 287 Pages: 408-17
  • Peer Reviewed
• [Journal Article] Nifedipine ameliorates ischemia-induced revascularization in diet-induced obese mice (2012)
  • Author(s): Kito T, Shibata R, Kondo M, Yamamoto T, Suzuki H, Ishii M and Murohara T
  • Journal Title: American journal of hypertension Volume: 25 Pages: 401-6
  • Peer Reviewed
• [Journal Article] CTRP9 protein protects against myocardial injury following ischemia-reperfusion through AMP-activated protein kinase (AMPK)-dependent mechanism (2012)
  • Author(s): Kambara T, Ohashi K, Shibata R, Ogura Y,Maruyama S, Enomoto T, Uemura Y, Shimizu Y,Yuasa D, Matsuo K, Miyabe M, Kataoka Y, Murohara T and Ouchi N
  • Journal Title: The Journal of biological chemistry Volume: 287 Pages: 18965-73
  • Peer Reviewed
• [Journal Article] Regulation of adipolin/CTRP12 cleavage by obesity (2012)
  • Author(s): Enomoto T, Shibata R, Ohashi K, Kambara T,Kataoka Y, Uemura Y, Yuasa D, Murohara T and Ouchi N
  • Journal Title: Biochemical and biophysical research communications Volume: 428 Pages: 155-9
  • Peer Reviewed
• [Journal Article] Cilostazol stimulates revascularisation in response to ischaemia via an enos-dependent mechanism (2012)
  • Author(s): Hori A, Shibata R, Morisaki K, Murohara T, Komori K
  • Journal Title: Eur J Vasc Endovasc Surg Volume: 43 Pages: 62-65
  • Peer Reviewed
• [Journal Article] Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical animal models. (2012)
  • Author(s): Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T
  • Journal Title: Circulation Volume: 14 Pages: 1728-38
  • Peer Reviewed
• [Journal Article] Omentin as a novel biomarker of metabolic risk factors. (2012)
  • Author(s): Shibata R, Ouchi N, Takahashi R, Terakura Y, Ohashi K, Ikeda N, Higuchi A, Terasaki H, Kihara S, Murohara T.
  • Journal Title: Diabetology & metabolic syndrome Volume: 4 Pages: 37-37
  • Peer Reviewed
• [Journal Article] Comparative angiogenic activities of induced pluripotent stem cells derived from young and old mice. (2012)
  • Author(s): Suzuki H, Shibata R, Kito T, Yamamoto T, Ishii M, Nishio N, Ito S, Isobe K, Murohara T.
  • Journal Title: PloS one. Volume: 7
  • Peer Reviewed
• [Journal Article] Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells. (2012)
  • Author(s): Shimizu Y, Shibata R, ShintaniS, Ishii M, Murohara T.
  • Journal Title: J. Am. Heart Assoc Volume: 1
  • Peer Reviewed
• [Journal Article] Nifedipine ameliorates ischemia-induced revascularization in diet-induced obese mice. (2012)
  • Author(s): Kito T, Shibata R, Kondo M, Yamamoto T, Suzuki H, Ishii M, Murohara T.
  • Journal Title: Am J Hypertens. Volume: 25 Pages: 401-406
  • Peer Reviewed
• [Journal Article] Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism (2012)
  • Author(s): Maruyama S, Shibata R, Kikuchi R, Izumiya Y, Rokutanda T, Araki S, Kataoka Y, Ohashi K, Daida H, Kihara S, Ogawa H, Murohara T, Ouchi N.
  • Journal Title: J Biol Chem Volume: 287 Pages: 408-417
• [Journal Article] Ctrp9 protein protects against myocardial injury following ischemia-reperfusion through amp-activated protein kinase (ampk)-dependent mechanism. (2012)
  • Author(s): Kambara T, Ohashi K, Shibata R, Ogura Y, Maruyama S, Enomoto T, Uemura Y, Shimizu Y, Yuasa D, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N.
  • Journal Title: J Biol Chem Volume: 287 Pages: 18965-18973
  • Peer Reviewed
• [Journal Article] Regulation of adipolin/ctrp12 cleavage by obesity. (2012)
  • Author(s): Enomoto T, Shibata R, Ohashi K, Kambara T, Kataoka Y, Uemura Y, Yuasa D, Murohara T, Ouchi N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 428 Pages: 155-159
  • Peer Reviewed
• [Journal Article] Adipose-derived factor ctrp9 attenuates vascular smooth muscle cell proliferation and neointimal formation (2012)
  • Author(s): Uemura Y, Shibata R, Ohashi K, Enomoto T, Kambara T, Yamamoto T, Ogura Y, Yuasa D, Joki Y, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N.
  • Journal Title: FASEB J Volume: 27 Pages: 25-33
  • Peer Reviewed
• [Journal Article] Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population (2011)
  • Author(s): Tanimura D, Shibata R, Izawa H, Hirashiki A,Asano H, Murase Y, Miyata S, Nakatochi M,Ouchi N, Ichihara S, Yasui K, Yoshida T, Naruse K, Matsubara T and Yokota M.
  • Journal Title: European journal of human genetics : EJHG Volume: 19 Pages: 262-9
  • Peer Reviewed
• [Journal Article] Association of a fat-derived plasma protein omentin with carotid artery intima-media thickness in apparently healthy men (2011)
  • Author(s): Shibata R, Takahashi R, Kataoka Y, Ohashi K,Ikeda N, Kihara S, Murohara T and Ouchi N
  • Journal Title: Hypertension research Volume: 34 Pages: 1309-12
  • NAID: 10030278035
  • Peer Reviewed
• [Journal Article] Circulating omentin is associated with coronary artery disease in men (2011)
  • Author(s): Shibata R, Ouchi N, Kikuchi R, Takahashi R,Takeshita K, Kataoka Y, Ohashi K, Ikeda N,Kihara S and Murohara T
  • Journal Title: Atherosclerosis Volume: 219 Pages: 811-4
  • Peer Reviewed
• [Journal Article] Adiponectin ameliorates doxorubicin-induced cardiotoxicity through Akt protein-dependent mechanism (2011)
  • Author(s): Maruyama 5, Shibata R, Ohashi K, Ohashi T,Daida H, Walsh K, Murohara T and Ouchi N
  • Journal Title: The Journal of biological chemistry Volume: 286 Pages: 82790-800
  • Peer Reviewed
• [Journal Article] Adipolin/Clqdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism (2011)
  • Author(s): Enomoto T, Ohashi K, Shibata R Higuchi A, Maruyama S, Izumiya Y, Walsh K, Murohara T and Ouchi N
  • Journal Title: The Journal of biological chemistry Volume: 286 Pages: 34552-8
  • Peer Reviewed
• [Journal Article] Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling (2011)
  • Author(s): Essick EE, Ouchi N, Wilson RAT, Ohashi K,Ghobrial J, Shibata R, Pimentel DR and Sam F
  • Journal Title: American journal of physiology Heart and circulatory physiology Volume: 301
  • Peer Reviewed
• [Journal Article] Association of adiponectin with carotid arteriosclerosis in predialysis chronic kidney disease (2011)
  • Author(s): Hayashi M, Shibata R, Takahashi H, Ishii H,Aoyama T, Kasuga H, Yamada S, Ohashi K,Maruyama S, Matsuo S, Ouchi N, Murohara T and Toriyama T
  • Journal Title: American journal of nephrology Volume: 34 Pages: 249-55
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid prevents atrial fibrillation associated with heart failure in a rabbit model (2011)
  • Author(s): Kitamura K, Shibata R Tsuji Y, Shimano M,Inden Y and Murohara T
  • Journal Title: American journal of physiology Heart and circulatory physiology Volume: 300
  • Peer Reviewed
• [Journal Article] Association of adiponectin with carotid arteriosclerosis in predialysis chronic kidney disease. (2011)
  • Author(s): Hayashi M, Shibata R, Takahashi H, Ishii H, Aoyama T, Kasuga H, Yamada S, Ohashi K, Maruyama S, Matsuo S, Ouchi N, Murohara T, Toriyama T.
  • Journal Title: Am J Nephrol Volume: 34 Pages: 249-255
  • Peer Reviewed
• [Journal Article] Adiponectin ameliorates doxorubicin-induced cardiotoxicity through Akt protein-dependent mechanism. (2011)
  • Author(s): Maruyama S, Shibata R, Ohashi K, Ohashi T, Daida H, Walsh K, Murohara T, Ouchi N.
  • Journal Title: J Biol Chem Volume: 286 Pages: 3279-800
  • Peer Reviewed
• [Journal Article] Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling. (2011)
  • Author(s): Essick EE, Ouchi N, Wilson RM, Ohashi K, Ghobrial J, Shibata R, Pimentel DR, Sam F.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 301 Pages: 984-93
  • Peer Reviewed
• [Journal Article] Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population. (2011)
  • Author(s): Tanimura D, Shibata R, Izawa H, Hirashiki A, Asano H, Murase Y, Miyata S, Nakatochi M, Ouchi N, Ichihara S, Yasui K, Yoshida T, Naruse K, Matsubara T, Yokota M.
  • Journal Title: Eur J Hum Genet. Volume: 19 Pages: 262-9
  • Peer Reviewed
• [Journal Article] Pioglitazone prevents intimal hyperplasia in experimental rabbit vein grafts. (2011)
  • Author(s): Morisaki K, Shibata R, Takahashi N, Ouchi N, Maehara Y, Murohara T, Komori K.
  • Journal Title: J Vasc Surg Volume: 54 Pages: 1753-9
  • Peer Reviewed
• [Journal Article] Circulating omentin is associated with coronary artery disease in men. (2011)
  • Author(s): Shibata R, Ouchi N, Kikuchi R, Takahashi R, Takeshita K, Kataoka Y, Ohashi K, Ikeda N, Kihara S, Murohara T.
  • Journal Title: Atherosclerosis Volume: 219 Pages: 811-4
  • Peer Reviewed
• [Presentation] 幹細胞を用いた心血管病治療法の開発 (2014)
  • Author(s): 柴田玲 室原豊明
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都市 国立京都国際会議場
  • Invited
• [Presentation] エイジングとアディポサイトカイン (2013)
  • Author(s): 柴田玲 大内乗有、室原豊明
  • Organizer: 脳心血管抗加齢研究会2013
  • Place of Presentation: 大阪市梅田スカイビル
  • Year and Date: 2013-12-14
  • Invited
• [Presentation] エイジングとアディポサイトカイン (2013)
  • Author(s): 柴田玲 大内乗有、室原豊明
  • Organizer: 脳心血管抗加齢研究会
  • Place of Presentation: 大阪市 梅田スカイビル
  • Invited
• [Presentation] iPS細胞を用いた血管病治療法の開発 (2013)
  • Author(s): 柴田玲 室原豊明
  • Organizer: 第21回日本血管生物医学学会学術集会
  • Place of Presentation: 大阪市 千里阪急ホテル
  • Invited
• [Presentation] アディポサイトカインによる心血管リモデリング制御機構の解明と治療への応用に関する研究 (2013)
  • Author(s): 柴田玲
  • Organizer: 第17回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪市 千里ライフサイエンスセンター
  • Invited
• [Presentation] 血管障害とアンチエイジング (2012)
  • Author(s): 柴田玲 大内乗有、室原豊明
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋市 名古屋キャッスルホテル
  • Year and Date: 2012-09-20
  • Invited
• [Presentation] アディポサイトカインと血管新生 (2012)
  • Author(s): 柴田玲 大内乗有、室原豊明
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋市名古屋市国際会議場
  • Year and Date: 2012-04-19
  • Invited
• [Presentation] アディポサイトカインと血管新生 (2012)
  • Author(s): 柴田玲 大内乗有、室原豊明
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 血管障害とアンチエイジング (2012)
  • Author(s): 柴田玲 大内乗有、室原豊明
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Association of a fat-derived hormone"omentin"with coronary artery disease in men (2011)
  • Author(s): Shibata R, Ouchi N, Kikuchi R, Takahashi R, Takeshita K, Kataoka Y, Ohashi K, Ikeda N, Murohara T
  • Organizer: The 84th Scientific Sessions of American Heart Association
  • Place of Presentation: Orland, USA
  • Year and Date: 2011-11-14
  • Invited
• [Presentation] Adiponectin and ischemic heart disease (2011)
  • Author(s): Shibata R
  • Organizer: The 41th Annual Convention and Scientific Session, Taiwan Society of Cardiology
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2011-05-14
  • Invited
• [Book] 脂肪組織と循環器疾患,カラー版 循環器病学 アップデート版1 (2013)
  • Author(s): 柴田玲、大内乗有、室原豊明
• [Book] アディポサイトカインと再生医療,循環器再生医学の現状と展望(室原豊明編) (2011)
  • Author(s): 柴田玲、室原豊明
• [Remarks]
  • URL: http://www.med.naoa-u.ac.jp/iunnai/junnai/
• [Patent(Industrial Property Rights)] 新規生理活性ペプチド及びその用途 (2014)
  • Inventor(s): 室原豊明、大内乗有、柴田玲、大橋浩二、関真美、土肥武
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-18
  • Overseas
• [Patent(Industrial Property Rights)] 新規生理活性ペプチド及びその用途 (2014)
  • Inventor(s): 室原豊明、大内乗有、柴田玲、その他
  • Industrial Property Rights Holder: 室原豊明、大内乗有、柴田玲、その他
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-18
• [Patent(Industrial Property Rights)] アディポネクチン蛋白の冠動脈内投与法による心筋梗塞治療の開発 (2013)
  • Inventor(s): 柴田玲、室原豊明
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-11
  • Overseas
• [Patent(Industrial Property Rights)] 生体組織を活性化する方法及びその装置 (2011)
  • Inventor(s): 山本徳則、柴田玲、淵真吾、竹田美和、鈴木哲、室原豊明、後藤百万、石井正和
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2011-12-15
  • Overseas