Functional roles of proline/arginine-rich end leucine-rich repeat protein (PRELP) in adipocytes

• Project/Area Number: 16K09783
• 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: Eguchi Jun 岡山大学, 大学病院, 講師 (60616366)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: メタボリックシンドローム / 脂肪組織 / 脂肪細胞 / インスリン抵抗性

Outline of Final Research Achievements

PRELP belongs to the family of leucine-rich repeat proteins, which are characterized by a series of adjacent leucine-rich motifs flanked by disulfide-bounded domains. In the present study, we show that PRELP expression is up-regulated in adipocytes of obesity mice. PRELP reduction in 3T3-L1 adipocytes leads to insulin-stimulated glucose uptake. To determine functions of PRELP, we generated adipocyte-specific PRELP transgenic mice. Adipose-specific overexpression of PRELP results in the development of adipose tissue fibrosis and insulin resistance on high fat diet without difference of body weight and adiposity. This phenotype is associated with increased inflammation and decreased insulin signaling in adipose tissue. Furthermore, we find that global Prelp deficient mice are protected from adipose tissue fibrosis and insulin resistance associated with high fat feeding. These data suggest that PRELP might play a key role in the development of adipose tissue remodeling in obesity.

Academic Significance and Societal Importance of the Research Achievements

メタボリックシンドロームにおいては体内に脂肪組織が過剰に蓄積し, 過剰に蓄積した脂肪組織中では, 慢性的に炎症が起こっている。この慢性炎症が脂肪組織の繊維化を誘導し, 全身のインスリン抵抗性, 種々の代謝異常を引き起こす。脂肪組織の繊維化を軽減, もしくは治癒させることは, 国民の健康維持、増進に有用である。そのためには, 脂肪組織の繊維化発症に関わる病態を解明する必要があるが, 未だ不明な点が多い。本研究は, Prelpが脂肪組織の繊維化発症に関与している可能性を示した。メタボリックシンドロームの有効な治療薬開発の糸口になる可能性がある。

Research Products

• [Journal Article] GPIHBP1 autoantibody syndrome during interferon β1a treatment. (2019)
  • Author(s): Eguchi J, Miyashita K, Fukamachi I, Nakajima K, Murakami M, Kawahara Y, Yamashita T, Ohta Y, Abe K, Nakatsuka A, Mino M, Takase S, Okazaki H, Hegele RA, Ploug M, Hu X, Wada J, Young SG, Beigneux AP.
  • Journal Title: J Clin Lipidol Volume: 13 Issue: 1 Pages: 62-69
  • DOI: 10.1016/j.jacl.2018.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. (2018)
  • Author(s): Shibata Y, Nakatsuka A, Eguchi J, Miyamoto S, Masuda Y, Awazawa M, Takaki A, Yoshida R, Yagi T, Wada J.
  • Journal Title: J Med Case Rep. Volume: 12 Issue: 1 Pages: 368-368
  • DOI: 10.1186/s13256-018-1901-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy (2018)
  • Author(s): Tanaka Keiko、Sugiyama Hitoshi、Yamanari Toshio、Mise Koki、Morinaga Hiroshi、Kitagawa Masashi、Onishi Akifumi、Ogawa-Akiyama Ayu、Tanabe Katsuyuki、Eguchi Jun、Ohmoto Yasukazu、Shikata Kenichi、Wada Jun
  • Journal Title: Nephrology Volume: 23 Issue: 9 Pages: 855-862
  • DOI: 10.1111/nep.13444
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of Novel Urinary Biomarkers for Predicting Renal Prognosis in Patients With Type 2 Diabetes by Glycan Profiling in a Multicenter Prospective Cohort Study: U-CARE Study 1. (2018)
  • Author(s): Mise K, Imamura M, Yamaguchi S, Teshigawara S, Tone A, Uchida HA, Eguchi J, Nakatsuka A, Ogawa D, Yoshida M, Yamada M, Shikata K, Wada J.
  • Journal Title: Diabetes Care. Volume: 41 Issue: 8 Pages: 1765-1775
  • DOI: 10.2337/dc18-0030
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of an enhanced recovery after surgery protocol in patients undergoing pancreaticoduodenectomy: A randomized controlled trial. (2018)
  • Author(s): Takagi K, Yoshida R, Yagi T, Umeda Y, Nobuoka D, Kuise T, Hinotsu S, Matsusaki T, Morimatsu H, Eguchi J, Wada J, Senda M, Fujiwara T.
  • Journal Title: Clinical Nutrition Volume: in press Issue: 1 Pages: 174-181
  • DOI: 10.1016/j.clnu.2018.01.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] メタボリックシンドロームにおける脂肪組織繊維化の発症分子機構 (2017)
  • Author(s): 江口 潤
  • Journal Title: 臨床病理 Volume: 65 Pages: 824-828
• [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] IRF3 promotes adipose inflammation and insulin resistance and represses browning. (2016)
  • Author(s): Kumari M, Wang X, Lantier L, Lyubetskaya A, Eguchi J, Kang S, Tenen D, Roh HC, Kong X, Kazak L, Ahmad R, Rosen ED.
  • Journal Title: J Clin Invest Volume: 126 Issue: 8 Pages: 2839-54
  • DOI: 10.1172/jci86080
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
• [Presentation] Roles of PRELP in adiocyte biology (2017)
  • Author(s): JUN EGUCHI
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone conference center
  • Year and Date: 2017-01-23
  • Int'l Joint Research
• [Presentation] 脂肪組織のリモデリングにおけるPRELPの病態生理的意義 (2017)
  • Author(s): 江口 潤
  • Organizer: 第38回日本肥満学会
• [Presentation] 脂肪組織リモデリングの制御因子の同定と機能解析 (2017)
  • Author(s): 江口 潤
  • Organizer: ConBio2017
  • Invited
• [Presentation] 脂肪組織のリモデリングにおけるPRELPの病態生理的意義 (2016)
  • Author(s): 江口 潤
  • Organizer: 第19回アディポサイエンス・シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンサー
  • Invited