Vaspin and its interacting molecules as therapeutic targets for metabolic syndrome

• Project/Area Number: 26293218
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Okayama University
• Principal Investigator: Wada Jun 岡山大学, 医歯(薬)学総合研究科, 教授 (30294408)
• Research Collaborator: NAKATSUKA Atsuko 岡山大学病院, 腎臓・糖尿病・内分泌内科, 助教 (00625949)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: メタボリックシンドローム / アディポカイン / セリンプロテアーゼ / 小胞体ストレス / 肥満症

Outline of Final Research Achievements

We identified vaspin (visceral adipose tissue-derived serine protease inhibitor) as a novel adlipokine. Vaspin inhibits insulin resistance, fatty liver, dyslipidemia and atherosclerosis in metabolic syndrome. Vaspin inhibits kallikrein 7 belonging to serine protease and increases glucagon-like peptide-1. We generated DNAJC1 (DnaJ homolog, subfamily C, member 1) conditional knockout mice and we demonstrated that they are therapeutic targets for metabolic syndrome.

Research Products

• [Journal Article] Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease. (2017)
  • Author(s): Wada N, Takaki A, Ikeda F, Yasunaka T, Onji M, Nouso K, Nakatsuka A, Wada J, Koike K, Miyahara K, Shiraha H, Yamamoto K, Okada H.
  • Journal Title: Hepatol Int Volume: 11 Issue: 1 Pages: 115-124
  • DOI: 10.1007/s12072-016-9773-y
  • Peer Reviewed / Open Access
• [Journal Article] Antiobesity action of ACAM by modulating the dynamics of cell adhesion and actin polymerization in adipocytes. (2016)
  • Author(s): Murakami K, Eguchi J, Hida K, Nakatsuka A, Katayama A, Sakurai M, Choshi H, Furutani M, Ogawa D, Takei K, Otsuka F, Wada J
  • Journal Title: Diabetes Volume: 65(5) Issue: 5 Pages: 1255-1267
  • DOI: 10.2337/db15-1304
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism. (2016)
  • Author(s): Tian Z, Miyata K, Kadomatsu T, Horiguchi H, Fukushima H, Tohyama S, Ujihara Y, Okumura T, Yamaguchi S, Zhao J, Endo M, Morinaga J, Sato M, Sugizaki T, Zhu S, Terada K, Sakaguchi H, Komohara Y, Takeya M, Takeda N, Araki K, Manabe I, Fukuda K, Otsu K, Wada J, Murohara T, Mohri S, Yamashita JK, Sano M, Oike Y.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 13016-13016
  • DOI: 10.1038/ncomms13016
  • NAID: 120006345014
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm. (2016)
  • Author(s): Takeuchi H, Okuyama M, Uchida HA, Kakio Y, Umebayashi R, Okuyama Y, Fujii Y, Ozawa S, Yoshida M, Oshima Y, Sano S, Wada J.
  • Journal Title: PLoS One. Volume: 11(10) Issue: 10 Pages: e0164015-e0164015
  • DOI: 10.1371/journal.pone.0164015
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice. (2016)
  • Author(s): Hatanaka T, Ogawa D, Tachibana H, Eguchi J, Inoue T, Yamada H, Takei K, Makino H, Wada J.
  • Journal Title: Pharmacol Res Perspect. Volume: 4(4) Issue: 4
  • DOI: 10.1002/prp2.239
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Innate immunity in diabetes and diabetic nephropathy. (2016)
  • Author(s): Wada J, Makino H.
  • Journal Title: Nat Rev Nephrol. Volume: 12(1) Issue: 1 Pages: 13-26
  • DOI: 10.1038/nrneph.2015.175
  • NAID: 120006358665
  • Peer Reviewed / Open Access
• [Journal Article] Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. (2016)
  • Author(s): Nakatsuka A, Matsuyama M, Yamaguchi S, Katayama A, Eguchi J, Murakami K, Teshigawara S, Ogawa D, Wada N, Yasunaka T, Ikeda F, Takaki A, Watanabe E, Wada J.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 21721-21721
  • DOI: 10.1038/srep21721
  • NAID: 120005728628
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis. (2015)
  • Author(s): Katayama A, Nakatsuka A, Eguchi J, Murakami K, Teshigawara S, Kanzaki M, Nunoue T, Hida K, Wada N, Yasunaka T, Ikeda F, Takaki A, Yamamoto K, Kiyonari H, Makino H, Wada J.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 16920-16920
  • DOI: 10.1038/srep16920
  • NAID: 120005697274
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes. (2015)
  • Author(s): Higuchi C, Nakatsuka A, Eguchi J, Teshigawara S, Kanzaki M, Katayama A, Yamaguchi S, Takahashi N, Murakami K, Ogawa D, Sasaki S, Makino H, Wada J.
  • Journal Title: Metabolism Volume: 64(4) Issue: 4 Pages: 489-97
  • DOI: 10.1016/j.metabol.2014.12.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes. (2015)
  • Author(s): Wang Y, Katayama A, Terami T, Han X, Nunoue T, Zhang D, Teshigawara S, Eguchi J, Nakatsuka A, Murakami K, Ogawa D, Furuta Y, Makino H, Wada J.
  • Journal Title: Metabolism Volume: 未定 Issue: 6 Pages: 677-88
  • DOI: 10.1016/j.metabol.2015.02.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] k factors for the development of glucocorticoid-induced diabetes mellitus. (2015)
  • Author(s): Katsuyama T, Sada KE, Namba S, Watanabe H, Katsuyama E, Yamanari T, Wada J, Makino H.
  • Journal Title: Diabetes Res Clin Pract Volume: 未定 Issue: 2 Pages: 273-279
  • DOI: 10.1016/j.diabres.2015.02.010
  • Peer Reviewed / Open Access
• [Presentation] Identification of an adipokine, vaspin, and its role in metabolic syndrome and diabetic nephropathy. (2016)
  • Author(s): Wada J
  • Organizer: 11th IDF-WPR Congress 2016 and 8th AASD Scientific Meeting
  • Place of Presentation: Taipei, Taiwan
  • Int'l Joint Research / Invited
• [Presentation] 肥満症と腎疾患 (2015)
  • Author(s): 和田淳、中司敦子、勅使川原早苗、村上和敏、江口潤
  • Organizer: 第36回日本肥満学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] Tim 44 （ translocase of inner mitochondrial membrane44）とメタボリックシンドロームにおける機能解析 (2015)
  • Author(s): 和田淳、王玉、片山晶博、寺見隆宏、布上朋和、中司敦子、村上和敏、勅使川原早苗、江口潤
  • Organizer: 第58回日本糖尿病学会総会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-22
• [Presentation] メタボリックシンドロームに伴う脂肪肝炎とPemtの意義 (2014)
  • Author(s): 中司敦子、村上和敏、勅使河原早苗、片山晶博、布上朋和、天田雅文、山口哲史、江口潤、和田淳
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎
  • Year and Date: 2014-10-25
• [Presentation] 脂肪肝炎におけるPemtの意義 (2014)
  • Author(s): 中司敦子、松山誠、村上和敏、勅使川原早苗、江口潤、小川大輔、高木章乃夫、福島正樹、山本和秀、槇野博史、和田淳
  • Organizer: 第１回肝臓と糖尿病・代謝研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-04
• [Presentation] メタボリックシンドロームにおけるphosphatidylethanolamine N-methyltransferase（PEMT）の意義 (2014)
  • Author(s): 中司 敦子、和田 淳、村上 和敏、勅使川原 早苗、片山 晶博、渡邊 真由、樋口 千草、天田 雅文、布上 朋和、江口 潤、小川 大輔、槇野 博史
  • Organizer: 第57回日本糖尿病学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-24