Identification of a novel protein that regulates adipose tissue dysfunction and its pathophysiological significance

• Project/Area Number: 20K08908
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Okayama University
• Principal Investigator: Eguchi Jun 岡山大学, 医歯薬学域, 准教授 (60616366)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脂肪組織 / メタボリックシンドローム / インスリン抵抗性 / 脂肪細胞

Outline of Research at the Start

メタボリックシンドロームは2型糖尿病、動脈硬化性疾、睡眠時無呼吸症候群、認知症など様々な疾患の温床となる。メタボリックシンドロームにおける内蔵脂肪蓄積型肥満においては、過栄養により肥大した脂肪細胞が脂肪組織内の慢性炎症や繊維化を誘導していると考えられている。本研究では、Ring finger protein 14 (RNF14)の脂肪細胞における役割を検討することによって、メタボリックシンドロームの有効な治療薬開発のための新たな創薬ターゲットを探索することを目的とする。

Outline of Final Research Achievements

In order to find a treatment for metabolic syndrome, we analyzed the function of RNF14, which is down-regulated during the differentiation of mouse progenitor adipocytes 3T3-L1cells. The expression of RNF14 was upregulated in fasting mouse adipose tissue. Furthermore, in cultured adipocytes, RNF14 promotes lipolysis, and mice systemically deficient in RNF14 showed increased adipose tissue volume and worsened systemic insulin resistance, suggesting that RNF14 is involved in the development of various diseases associated with metabolic syndrome.

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, RNF14が脂肪組織の機能不全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] Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle (2022)
  • Author(s): Tenta M, Eguchi J, Wada J.
  • Journal Title: Acta Medica Okayama Volume: 76 Issue: 3 Pages: 235-245
  • DOI: 10.18926/AMO/63717
  • URL: https://ousar.lib.okayama-u.ac.jp/63717
  • Peer Reviewed / Open Access
• [Journal Article] Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study. (2022)
  • Author(s): Kurooka N, Eguchi J, Murakami K, Kamei S, Kikutsuji T, Sasaki S, Seki A, Yamaguchi S, Nojima I, Watanabe M, Higuchi C, Katayama A, Uchida HA, Nakatsuka A, Shikata K, Wada J.
  • Journal Title: J Clin Lipidol. Volume: 22 Issue: 2 Pages: 21-26
  • DOI: 10.1016/j.jacl.2022.01.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4. (2022)
  • Author(s): Yamaguchi S, Zhang D, Katayama A, Kurooka N, Sugawara R, Albuayjan HHH, Nakatsuka A, Eguchi J, Wada J.
  • Journal Title: Front Endocrinol (Lausanne). Volume: 12 Pages: 750261-750261
  • DOI: 10.3389/fendo.2021.750261
  • NAID: 120007188342
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study (2022)
  • Author(s): Matsuoka-Uchiyama Natsumi、Uchida Haruhito A.、Okamoto Shugo、Onishi Yasuhiro、Katayama Katsuyoshi、Tsuchida-Nishiwaki Mariko、Takeuchi Hidemi、Takemoto Rika、Hada Yoshiko、Umebayashi Ryoko、Kurooka Naoko、Tsuji Kenji、Eguchi Jun、Nakajima Hirofumi、Shikata Kenichi、Wada Jun
  • Journal Title: Journal of Diabetes Research Volume: 2022 Pages: 1-12
  • DOI: 10.1155/2022/3157841
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control. (2021)
  • Author(s): Zhang D, Yamaguchi S, Zhang X, Yang B, Kurooka N, Sugawara R, Albuayjan HHH, Nakatsuka A, Eguchi J, Hiyama TY, Kamiya A, Wada J.
  • Journal Title: Front Endocrinol (Lausanne). Volume: 12 Pages: 727915-727915
  • DOI: 10.3389/fendo.2021.727915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor‐induced diabetes mellitus: A report of two cases (2021)
  • Author(s): Fujiwara Noriko、Watanabe Mayu、Katayama Akihiro、Noda Yohei、Eguchi Jun、Kataoka Hitomi、Kagawa Shunsuke、Wada Jun
  • Journal Title: Clinical Case Reports Volume: 9 Issue: 9
  • DOI: 10.1002/ccr3.4574
  • NAID: 120007161107
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2. (2021)
  • Author(s): Nunoue T, Yamaguchi S, Teshigawara S, Katayama A, Nakatsuka A, Eguchi J, Niki T, Wada J.
  • Journal Title: Sci Rep. Volume: 16 Issue: 1 Pages: 5991-5991
  • DOI: 10.1038/s41598-021-85080-1
  • NAID: 120007004155
  • Peer Reviewed / Open Access
• [Journal Article] A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease (2021)
  • Author(s): Nakatsuka A, Yamaguchi S, Eguchi J, Kakuta S, Iwakura Y, Sugiyama H, Wada J.
  • Journal Title: Commun Biol . Volume: 4 Issue: 1 Pages: 373-373
  • DOI: 10.1038/s42003-021-01902-y
  • NAID: 120007004153
  • Peer Reviewed / Open Access
• [Journal Article] Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis (2020)
  • Author(s): Nojima I, Eikawa S, Tomonobu N, Hada Y, Kajitani N, Teshigawara S, Miyamoto S, Tone A, Uchida HA, Nakatsuka A, Eguchi J, Shikata K, Udono H, Wada J.
  • Journal Title: Sci Rep. Volume: 10 Issue: 1 Pages: 14928-14928
  • DOI: 10.1038/s41598-020-71946-3
  • NAID: 120006891215
  • Peer Reviewed / Open Access