Strategy for the treatment of CKD-induced sarcopenia based on the crosstalk between myokine and uremic toxins

• Project/Area Number: 18K15069
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Keio University
• Principal Investigator: ENOKI YUKI 慶應義塾大学, 薬学部(芝共立), 助教 (50813854)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 慢性腎臓病 / サルコペニア / 尿毒症物質 / 筋作動因子 / apelin

Outline of Final Research Achievements

In a mouse model of chronic kidney disease (CKD), the skeletal muscle weight and the cross-sectional area of the muscle fiber appeared to gradually decrease after the CKD surgery; expression of apelin-a skeletal muscle-derived secretory factor also decreased in the skeletal muscles. The administration of charcoal, a uremic toxin adsorbent, suppressed the decrease in apelin and skeletal muscle mass. Furthermore, apelin suppressed the decrease in skeletal muscle mass in CKD mice. The findings suggest that uremic toxin-mediated downregulation of apelin may play an important role in the pathophysiology of CKD-induced sarcopenia. Apelin, therefore could be a promising therapeutic target for CKD-induced sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

本研究は、慢性腎臓病に伴う骨格筋の減少（サルコペニア）の病態発症メカニズムの解明と病態メカニズムに基づいた新たなサルコペニア治療法の確立を目的としている。慢性腎臓病の病態の進行に伴って、骨格筋の量や機能を維持するために必要な生理因子（アペリン）が低下することを明らかにし、このアペリンを補充することで慢性腎臓病によるサルコペニアを治療、予防することが可能である可能性を明らかにした。

Research Products

• [Journal Article] Indoxyl sulfate contributes to adipose tissue inflammation through the activation of NADPH oxidase (2020)
  • Author(s): Shoma Tanaka*, Hiroshi Watanabe*,#, Takehiro Nakano, Tadashi Imafuku, Hiromasa Kato, Kai Tokumaru, Nanaka Arimura, Yuki Enoki, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Toru Maruyama# *equal contribution; #equal correspondence
  • Journal Title: Toxins (Basel) Volume: 5;12(8): Issue: 8 Pages: 502-502
  • DOI: 10.3390/toxins12080502
  • Peer Reviewed / Open Access
• [Presentation] 慢性腎臓病誘発サルコペニアに対するapelinの有用性評価 (2021)
  • Author(s): 永井智也、榎木裕紀、中村秀明、田口和明、松元一明
  • Organizer: 日本薬学会第141年会
• [Presentation] 慢性腎臓病病態の骨格筋萎縮における 尿毒素の関与と新規治療戦略に関する検討 (2018)
  • Author(s): 榎木裕紀、渡邊博志、荒毛里歩、異島優、松元一明、小田切優樹、丸山徹
  • Organizer: 日本老年薬学会
• [Book] Uremic Toxins and Organ Failure (2020)
  • Author(s): Hiroshi Watanabe, Hiromasa Kato, Yuki Enoki, Hitoshi Maeda, Toru Maruyama
  • Total Pages: 180
  • Publisher: Springer
  • ISBN: 9789811577932