The pathophysiology in hypoadiponectinemia

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Showa University
• Principal Investigator: NAKANO Yasuko 昭和大学, 薬学部, 教授 (20155790)
• Co-Investigator(Kenkyū-buntansha): NEGORO Takaharu 昭和大学, 薬学部、薬学研究科, 講師 (70218270)
• Co-Investigator(Renkei-kenkyūsha): TANIOKA Toshihiro 昭和大学, 薬学部、薬学研究科, 助教 (80360585)
• Project Period (FY): 2011 – 2013
• Keywords: 炎症 / アディポネクチン / マクロファージ / 高分子量アディポネクチン / 易炎症性 / 低アディポネクチン血症

Research Abstract

Adiponectin is a protein which is secreted to blood from adipose tissue and has anti-inflammatory, anti-diabetes and anti-atherosclerosis functions. Decreased plasma adiponectin levels are well associated with components of the metabolic syndrome like diabetes.
When macrophage cell line RAW264.7 cells were treated for 48 hours with low or high concentration of adiponectin and gene expressions were compared, there was no dramatic difference, but the expression level of many genes involved in inflammation and immune system were different. Using genetically engineered mice with low blood adiponectin concentration, we found that expression of IL-10 in macrophages, which suppresses the inflammation, decreased to 1/15 and the adipose tissue is prone to inflammation compared to wild type mice. We are planning to search medicines to ameliorate this easy-to-inflame condition under low adiponectin concentration.

Research Products

• [Journal Article] Potentiated macrophage activation by acid sensing under low adiponectin levels (2014)
  • Author(s): Negoro T, Kin M, Takuma A, Saito K, Shimizu S, Nakano Y
  • Journal Title: Mol Immunol Volume: vol.57 Pages: 141–150
  • DOI: 10.1016/j.molimm.2013.08.015
  • Peer Reviewed
• [Journal Article] Metformin modulates GLP-1- and GIP-mediated intracellular signaling under normoglycemic conditions (2013)
  • Author(s): Shinmura K, Negoro T, Shimizu S, Roncador G, Hirano T, Nakano Y
  • Journal Title: Open J Endocri Metab Dis Volume: vol.3 Pages: 263-270
  • DOI: 10.4236/ojemd.2013
  • Peer Reviewed
• [Journal Article] Adiponectin enhances calcium-dependency of mouse bladder contraction mediated by protein kinase Cαexpression (2013)
  • Author(s): Nobe K, Fujii A, Saito K, Negoro T, Ogawa Y, Nakano Y, Hashimoto T, Honda K
  • Journal Title: J Pharmacol Exp Ther Volume: vol.345 Pages: 62-68
  • DOI: 10.1124/jpet.112.202028
  • Peer Reviewed
• [Journal Article] Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial ischaemia/reperfusion injury (2013)
  • Author(s): Hiroi T, Wajima T, Negoro T, Ishii M, Yasuko Nakano, Kiuchi K, Mori Y, and Shimizu S
  • Journal Title: Cardiovasc Res Volume: vol.97 Pages: 271-281
  • DOI: 10.1093/cvr/cvs332
  • Peer Reviewed
• [Journal Article] Multiple SNPs in Intron 41 of Thyroglobulin Gene Are Associated with Autoimmune Thyroid Disease in the Japanese Population (2012)
  • Author(s): Ban Y, Tozaki T, Taniyama M, Skrabanek L, Nakano Y, Ban Y, Hirano T
  • Journal Title: PLoS ONE Volume: vol.7 Pages: e37501
  • DOI: 10.1371/journal.pone.0037501
  • Peer Reviewed
• [Journal Article] Impaired Ca2+ regulation of CD4+CD25+ regulatory T cells from pediatric asthma (2011)
  • Author(s): Yamamoto Y, Negoro T, Hoshi A, Wakagi A, Shimizu S, Banham A H, Ishii M, Akiyama H, Kiuchi K, Sunaga S, Tobe T, Roncador G, Itabashi K, and Nakano Y
  • Journal Title: Int Arch Allergy Immunol Volume: vol.156 Pages: 148-158
  • DOI: 10.1159/000322845
  • Peer Reviewed
• [Journal Article] The effect of adiponectin on the cardiac allograft vasculopathy (2011)
  • Author(s): Ishihara T, Haraguchi G, Konishi M, Ohigashi H, Saito K, Nakano Y, and Isobe M
  • Journal Title: Circ J Volume: vol.75 Pages: 2005–2012
  • DOI: 10.1253/circj.CJ-10-0879
  • Peer Reviewed
• [Presentation] アディポネクチンによる抗炎症作用の解析 (2013)
  • Author(s): 谷岡利裕,躰長義直,山田倫世,根来孝治,中野泰子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20131203-06
• [Presentation] Modulation of incretin actions in pancreaticβ-cells by metformin (2013)
  • Author(s): Shinmura K, Negoro T, Nakano Y, Hirano T
  • Organizer: 49th Annual meeting of the European association for the study of diabetes
  • Place of Presentation: スペイン
  • Year and Date: 20130923-27
• [Presentation] メトホルミンによる膵β細胞のインクレチン刺激細胞内シグナル制御機構の検討 (2013)
  • Author(s): 新村京子,根来孝治,中野泰子,平野勉
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Year and Date: 20130516-18
• [Presentation] アディポネクチンにより誘導されるIRF-7が破骨細胞分化を制御する (2012)
  • Author(s): 谷岡利裕、石直南、杉原希美、平川琴美、石原伸恵、根来孝治、中野泰子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 20121214-16
• [Presentation] 関節リウマチにおけるアディポネクチンの生理的機能解明 (2012)
  • Author(s): 秋山晴代,嶋田紘也,齊藤清美,根来孝治,中野泰子
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] Molecular Structure and Function of High-Molecular-Weight Adiponectin (2012)
  • Author(s): Nakano Y
  • Organizer: The 64th Fujihara Seminar International Symposium on Adiponectin Biology and Medicine
  • Place of Presentation: 苫小牧
  • Year and Date: 20120804-07
  • Invited
• [Presentation] Potentiated macrophage activation by acid sensing under low adiponectin levels (2012)
  • Author(s): Negoro T, Akiyama H, Tanioka T, Saito K, Shimizu S, and Nakano Y
  • Organizer: The 64th Fujihara Seminar International Symposium on Adiponectin Biology and Medicine
  • Place of Presentation: 苫小牧
  • Year and Date: 20120804-07
• [Presentation] Effect of Lower adiponectin concentration exert a harmful influence (2012)
  • Author(s): Saito K, Negoro T, Sato H, Nakano Y
  • Organizer: The 64th Fujihara Seminar International Symposium on Adiponectin Biology and Medicine
  • Place of Presentation: 苫小牧
  • Year and Date: 20120804-07
• [Presentation] Effect of RACK1 on impaired functions of CD4+CD25+ regulatory T cells from asthma subjects (2011)
  • Author(s): Negoro T, Shimizu S, Narushima M, Endo A, Tanioka T, Nakano Y
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 20111127-29
• [Presentation] iNOS Promotes Proteasome-Dependent Degradation of IRS-2 by Activating GSK-3βin Pancreaticβ-cells (2011)
  • Author(s): Tanioka T, Tamura Y, Mao J, Kitamura T, Negoro T, Nakano Y, Kaneki M
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 20110921-24
• [Presentation] Individual optimization of mizoribine dose to child-onset glomerular disease (2011)
  • Author(s): Abe Y, Fuke T, Hibino S,Mikawa T, Saito T, Watanabe S, Hisano M, Murayama J, Nakano Y and Itabashi K
  • Organizer: The 11th Asian Congress of Pediatric Nephrology
  • Place of Presentation: 福岡
  • Year and Date: 20110602-04
• [Presentation] アディポネクチンによる破骨細胞分化抑制機構の解明 (2011)
  • Author(s): 石直南、谷岡利裕、平川琴美、根来孝治、中野泰子
  • Organizer: 第55回日本薬学会関東支部大会
  • Place of Presentation: 千葉
  • Year and Date: 2011-10-08
• [Book] バイオ医薬品開発の基礎から次世代医薬品まで, 26章テーラーメードゲノム創薬 (2013)
  • Author(s): 中野泰子他22名, (西島正弘・川崎ナナ編)
  • Total Pages: 245-262
  • Publisher: (株)化学同人
• [Book] Bronchial asthma-Emerging therapeutic strategies、chapter 4 Immune mechanisms of childhood asthma, ISBN; 978-953-51-0140-6260 (2012)
  • Author(s): Negoro T, Yamamoto Y, Shimizu S, Banham AH, Roncador G, Wakabayashi H, Osabe T, Yanai T, Akiyama H, Itabashi K, Nakano Y, (Editor; Elizabeth Sapey)
  • Publisher: InTech
• [Remarks]
  • URL: http://www.showa-u.ac.jp/sch/pharm/major/medinfo/