The role of vaspin in metabolic syndrome associated renal disease

• Project/Area Number: 26461361
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Okayama University
• Principal Investigator: Nakatsuka Atsuko 岡山大学, 大学病院, 助教 (00625949)
• Research Collaborator: WADA Jun 岡山大学, 大学院医歯薬学総合研究科・腎・免疫・内分泌代謝内科学, 教授
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: メタボリックシンドローム / 慢性腎臓病 / アディポカイン / 糖尿病性腎症 / 小胞体ストレス / Vaspin / ライソゾーム

Outline of Final Research Achievements

We previously identified an adipokine, vaspin. In this study, we checked the beneficial role of vaspin in renal injury of metabolic syndrome. Vaspin transgenic(Tg) and vaspin-/- mice were fed with high fat high sucrose (HFHS) diet. At 30 weeks of age, prominent vacuolation in the kidney tissues of vaspin-/- mice under HFHS diet are observed, and it is meliorated in Tg mice. These vacuoles are toluidine blue positive and EM demonstrates lysosomal enlargement. TUNEL-positive apoptotic tubular cells increase in vaspin-/- mice fed with HFHS compared with Tg and wild type mice. Next, we investigated the streptozotocin(STZ) induced-diabetes model. In Tg mice, the dilatation and thinning of tubules induced by diabetes are ameliorated. TUNEL-positive apoptotic cells are increased in STZ induced diabetic vaspin-/- mice, while in Tg mice apoptosis was inhibited. It is suspected that vaspin ameliorate tubulointerstitial injury in diabetic and metabolic syndrome associated renal disease.

Research Products

• [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] 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] Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes. (2016)
  • Author(s): Wada J, Nakatsuka A.
  • Journal Title: Acta Med Okayama. Volume: 70(3) Pages: 151-8
  • NAID: 120005770682
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The anti-obesity 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: in press
  • Peer Reviewed / 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] Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. (2014)
  • Author(s): Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, Nakatsuka A, Eguchi J, Horiguchi CS, Nishii N, Yamada H, Takei K, Makino H.
  • Journal Title: PLoS One. Volume: 9
  • Peer Reviewed
• [Journal Article] Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy. (2014)
  • Author(s): Watanabe M, Nakatsuka A, Murakami K, Inoue K, Terami T, Higuchi C, Katayama A, Teshigawara S, Eguchi J, Ogawa D, Watanabe E, Wada J, Makino H.
  • Journal Title: PLoS One. Volume: 9
  • NAID: 120005723281
  • Peer Reviewed / Open Access
• [Presentation] A protective role of vaspin against proximal tubular cell injuries in diabetes mellitus (2017)
  • Author(s): Atsuko Nakatsuka, Satoshi Yamaguchi, Jun Eguchi, Jun Wada
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone resort conference center, Colorado, USA
  • Year and Date: 2017-01-24
  • Int'l Joint Research
• [Presentation] Vaspinの肥満書における腎障害抑制機序の解明 (2016)
  • Author(s): 中司敦子、山口哲志、柴田祐助、勅使川原早苗、江口潤、和田淳
  • Organizer: 第37回日本肥満学会
  • Place of Presentation: 東京ファッションタウンビル
  • Year and Date: 2016-10-07
• [Presentation] 糖尿病性腎症におけるVaspionの意義 (2016)
  • Author(s): 中司敦子、三瀬広記録、江口潤、和田淳
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-06-17
• [Presentation] A protective role of vaspin against proximal tubular cell injuries in diabetes mellitus (2016)
  • Author(s): Atsuko Nakatsuka and Jun Wada
  • Organizer: 第59回日本糖尿病学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-05-21
  • Invited
• [Presentation] 糖尿病腎症におけるvaspinの意義 (2016)
  • Author(s): 中司敦子、山口 哲士、柴田 祐助、勅使川原 早苗、江口 潤、和田 淳
  • Organizer: 第59回日本糖尿病学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-05-19
• [Presentation] 肥満関連腎症におけるvaspinの意義 (2015)
  • Author(s): 中司敦子、村上和敏、勅使川原早苗、山口哲志、柴田祐助、天田雅文、江口潤、和田淳
  • Organizer: 第36回日本肥満学会
  • Place of Presentation: 名古屋国際競技場
  • Year and Date: 2015-10-02
• [Presentation] PEMT deficiency promotes steatohepatitis through sustained apoptosis via clathrin heavy chain-p53 mediated transcriptional mechanisms. (2015)
  • Author(s): Atsuko Nakatsuka, Kazutoshi Murakami, Tomokazu Nunoue, Satoshi Yamaguchi, Jun Eguchi, Jun Wada
  • Organizer: American Diabetes Association’s 75th Scientific Sessions
  • Place of Presentation: The Boston Convention and Exhibition Center
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] メタボリックシンドロームにおけるphosphatidylethanolamine N-methyltransferase (PEMT)が関与する脂肪肝炎と肝再生機構 (2015)
  • Author(s): 中司敦子、村上和敏、勅使川原早苗、片山晶博、天田雅文、布上朋和、山口哲志、江口潤、小川大輔、和田淳
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ下関
  • Year and Date: 2015-05-21
• [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、勅使川原早苗、片山晶博、布上朋和、天田雅文、山口哲志、江口潤、和田淳
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: シーガイアコンベンションセンター
  • Year and Date: 2014-10-24
• [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回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Book] 糖尿病腎症進展のメカニズム 糖尿病腎症の治療のポイント (2016)
  • Author(s): 中司敦子、和田淳
  • Total Pages: 383
  • Publisher: 医薬ジャーナル社
• [Book] 新時代の臨床糖尿病学（上）―より良い血糖管理をめざして― (2016)
  • Author(s): 中司敦子、和田淳
  • Total Pages: 671
  • Publisher: 日本臨牀
• [Book] 医学のあゆみ (2014)
  • Author(s): 中司敦子､ 和田淳
  • Publisher: 医歯薬出版株式会社