The impact of ACAM/CLMP on the adipocytes differentiation and obesity through the primary ciliary machinery

• Project/Area Number: 26461362
• 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: Murakami Kazutoshi 岡山大学, 医学部, 客員研究員 (40620753)
• Research Collaborator: WADA JUN 岡山大学, 大学院医歯薬学総合研究科, 教授 ; EGUCHI JUN 岡山大学, 大学病院, 講師 ; NAKATSUKA ATSUKO 岡山大学, 大学病院, 助教
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 脂肪細胞 / メタボリックシンドローム / 肥満症 / 膜蛋白 / 接着分子 / アドヘレンスジャンクション / アクチン / アドへレンスジャンクション / 肥満 / 一次繊毛

Outline of Final Research Achievements

The excess of lipid accumulation and hypertrophy of adipocytes induces the abnormality of secretion of adipokines and hormones from adipocytes and causes metabolic syndrome and diabetes. We identified ACAM in 2005 from the visceral fat tissue of obese rats. It is a cell adhesion molecule responsible for the homophilic adhesion of the cells. In the transgemic mice overexpressing ACAM in adipocytes fed with a high fat and high sucrose diet were protected from the onset of obesity and diabetes. In transgemnic mice, ACAM is abundantly expressed on plasma membrane of mature adipocytes and associated with formation of Phalloidin-positive polymerized form of cortical actin (F-actin). By electron microscopy, the structure of zonula adherens was formed at interphase of adipocytes. The adhesion of adipocytes and formation of cortical actin prevent the adipocyte hypertrophy and development of obesity and diabetes.

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] 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] 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] 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
• [Presentation] The anti-obesity action of ACAM by modulating the dynamics of cell adhesion and actin polymerization in adipocytes. (2015)
  • Author(s): Kazutoshi Murakami, Jun Eguchi, Atsuko Nakatsuka, Tomokazu Nunoue, Satoshi Yamaguchi and Jun Wada
  • Organizer: 75th American Diabetes Association
  • Place of Presentation: Boston(アメリカ合衆国)
  • Year and Date: 2015-06-04
  • Int'l Joint Research
• [Presentation] 脂肪細胞における接着とアクチン重合を介したACAMの抗肥満作用 (2014)
  • Author(s): 村上和敏、和田淳、江口潤、中司敦子、槇野博史
  • 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（宮崎）
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] The anti-obesity action of ACAM by modulating the dynamics of cell adhesion and actin polymerization in adipocytes. (2014)
  • Author(s): 村上和敏、和田淳、江口潤、中司敦子、槇野博史
  • Organizer: インスリン抵抗性とメタボリックシンドローム研究会
  • Place of Presentation: ハイアットリージェンシー（東京）
  • Year and Date: 2014-07-05 – 2014-07-06
• [Presentation] 脂肪細胞における接着とアクチン重合を介したACAMの抗肥満作用 (2014)
  • Author(s): 村上和敏
  • Organizer: 第4回 Okayama Young Investigator’s Seminar
  • Place of Presentation: 岡山大学（岡山）
  • Year and Date: 2014-05-30
• [Presentation] ACAM (adipocyte adhesion molecule) /CLMPの一次繊毛機能を介した脂肪細胞分化と肥満症における意義 (2014)
  • Author(s): 村上和敏、和田淳、江口潤、中司敦子、槇野博史
  • Organizer: 第57回 日本糖尿病学会
  • Place of Presentation: 大阪国際会議場（大阪）
  • Year and Date: 2014-05-22 – 2014-05-24