Regulation of Notch signal pathway in adipogenesis

• Project/Area Number: 25461336
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nagoya University
• Principal Investigator: Takeshita Kyosuke 名古屋大学, 医学部附属病院, 講師 (70444403)
• Co-Investigator(Kenkyū-buntansha): SEI Kenbu 名古屋大学, 未来社会創造機構, 特任准教授 (30378228)
• Co-Investigator(Renkei-kenkyūsha): MUROHARA Toyoaki 名古屋大学, 医学系研究科, 教授 (90299503)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Notchシグナル / 脂肪組織 / 分化増殖 / 白色脂肪 / 脂肪細胞 / メタボリックシンドローム / メタボリック症候群

Outline of Final Research Achievements

Among four homologous Notch receptors, Notch1 plays critical roles in organogenesis but its role in adipogenesis is unknown. Body weight gain and adipose deposition were altered in Notch1 heterozygous deficient mice (N1+/-) compared to wild-type mice (WT) with the same intake. The inguinal white adipose tissue (WAT) from N1+/- showed changes in expression levels of growth factors and transcription factors which are involved in adipogenesis. Pharmacological Notch signal inhibition with LY411,575 and siRNA-mediated Notch1 knockdown alatered adipogenesis in 3T3-L1 preadipocytes (on submission). Taken together, Notch1 would be involved in adipogenesis to regulate diet-induced obesity.

Research Products

• [Journal Article] Identification of a novel missense mutation (563G>a) in the ABO gene associated with a Bel phenotype. (2016)
  • Author(s): Niwa R, Nakayama T, Ishii H, Fujita E, Ishiyama K, Matsuo T, Shimizu A, Gao S, Hayashi M, Katai A, Ando T, Takahashi M, Takeshita K, Takami A, Kato H.
  • Journal Title: Transfusion Volume: 未定 Issue: 5 Pages: 1242-3
  • DOI: 10.1111/trf.13507
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Angiotensin receptor blocker improves a stress-induced prothrombotic state in a murine model. (2016)
  • Author(s): Hayashi M, Takeshita K, Uchida Y, Yamamoto K, Matsushita T, Murohara T.
  • Journal Title: Blood Coagul Fibrinolysis. Volume: 27 Issue: 3 Pages: 358-60
  • DOI: 10.1097/mbc.0000000000000451
  • Peer Reviewed
• [Journal Article] Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy. (2016)
  • Author(s): Hirashiki A, Kondo T, Okumura T, Kamimura Y, Nakano Y, Fukaya K, Sawamura A, Morimoto R, Adachi S, Takeshita K, Murohara T.
  • Journal Title: Ann Noninvasive Electrocardiol. Volume: - Issue: 3 Pages: 263-271
  • DOI: 10.1111/anec.12308
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Admission Anemia on Coronary Microcirculation and Clinical Outcomes in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (2015)
  • Author(s): Uchida Y, Ichimiya S, Ishii H, Kanashiro M, Watanabe J, Hayano S, Suzuki S, Takeshita K, Sakai S, Amano T, Matsubara T, Murohara T.
  • Journal Title: International Heart Journal Volume: 56 Issue: 4 Pages: 381-388
  • DOI: 10.1536/ihj.15-006
  • NAID: 130005087571
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed
• [Journal Article] Impact of airflow limitation on carotid atherosclerosis in coronary artery disease patients. (2015)
  • Author(s): Hamrah MS, Suzuki S, Ishii H, Shibata Y, Tatami Y, Osugi N, Ota T, Kawamura Y, Tanaka A, Aso H, Takeshita K, Sakamoto J, Hasegawa Y, Murohara T.
  • Journal Title: Respiration. Volume: 89 Issue: 4 Pages: 322-8
  • DOI: 10.1159/000375313
  • Peer Reviewed
• [Journal Article] Cathepsin S Activity Controls Ischemia-Induced Neovascularization in Mice (2015)
  • Author(s): Li X, Cheng XW, Hu L, Wu HX, Hao CH, Shi GP, Jiang H, Zhu E, Inoue A, Huang Z, Sasaki T, Takeshita K, Okumura K, Murohara T, Kuzuya M
  • Journal Title: International Journal of Cardiology Volume: 183 Pages: 198-208
  • DOI: 10.1016/j.ijcard.2015.01.058
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance. (2014)
  • Author(s): Hayashi M, Takeshita K, Uchida Y, Yamamoto K, Kikuchi R, Nakayama T, Nomura E, Cheng XW, Matsushita T, Nakamura S, Murohara T.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e116163-e116163
  • DOI: 10.1371/journal.pone.0116163
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Does angiotensin receptor blockade ameliorate the prothrombotic tendency in hypertensive patients with atrial fibrillation? breaking the vicious cycle. (2014)
  • Author(s): Takeshita K, Murohara T.
  • Journal Title: Hypertens Res. Volume: - Issue: 6 Pages: 490-491
  • DOI: 10.1038/hr.2014.48
  • Peer Reviewed
• [Journal Article] Cardiopulmonary exercise testing to evaluate the exercise capacity of patients with inoperable chronic thromboembolic pulmonary hypertension: An endothelin receptor antagonist improves the peak PETCO2. (2014)
  • Author(s): Hirashiki A, Adachi S, Nakano Y, Kono Y, Shimazu S, Shimizu S, Morimoto R, Okumura T, Takeshita K, Yamada S, Murohara T, Kondo T.
  • Journal Title: Life Sci. Volume: - Issue: 2 Pages: 397-403
  • DOI: 10.1016/j.lfs.2014.03.009
  • Peer Reviewed / Open Access
• [Journal Article] Recovery of flow-mediated vasodilatation after repetitive measurements is involved in early vascular impairment: comparison with indices of vascular tone. (2014)
  • Author(s): Inaba H, Takeshita K, Uchida Y, Hayashi M, Okumura T, Hirashiki A, Yoshikawa D, Ishii H, Yamamoto K, Nakayama T, Hirayama M, Matsumoto H, Matsushita T, Murohara T
  • Journal Title: PLOS one Volume: 9(1) Issue: 1 Pages: 1-9
  • DOI: 10.1371/journal.pone.0083977
  • Peer Reviewed / Open Access
• [Presentation] Dipeptidyl peptidase-4 Inhibitor Ameliorates Stress-induced Glucose Metabolism Disorder and Prothrombotic State (2015)
  • Author(s): Kyosuke Takeshita, Maimaiti Yisireyili, Toyoaki Murohara
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2015-11-09
  • Int'l Joint Research
• [Presentation] Abstract 13062: Notch1 Signaling Regulates Adipogenesis in vivo (2013)
  • Author(s): Motoharu Hayashi, Nagoya university, Kyousuke Takeshita, and Toyoaki Murohara
  • Organizer: American Heart Association
  • Place of Presentation: ダラス 米国