Angiotensin Receptor Blockers Potentiate the Protective Effect of Branched-Chain Amino Acids on Skeletal Muscle Atrophy in Cirrhotic Rats

• Material Type: 博士論文
• Title: Angiotensin Receptor Blockers Potentiate the Protective Effect of Branched-Chain Amino Acids on Skeletal Muscle Atrophy in Cirrhotic Rats
• Author/Editor: Takeda, Soichi; Kaji, Kosuke; Nishimura, Norihisa; Enomoto, Masahide; Fujimoto, Yuki; Murata, Koji; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• Author Heading: Takeda, Soichi; Kaji, Kosuke; Nishimura, Norihisa; Enomoto, Masahide; Fujimoto, Yuki; Murata, Koji; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• Publication, Distribution, etc.: Wiley
• Publication Date: 2021-12
• Publication Date (W3CDTF): 2021-12
• Alternative Title: アンジオテンシン受容体拮抗薬は、肝硬変ラットの骨格筋萎縮に対して、分岐鎖アミノ酸製剤による保護効果を増強する。
• Periodical title: Molecular nutrition & food research.
• No. or year of volume/issue: 65 24
• Volume: 65
• Issue: 24
• Pages: e2100526-
• ISSN (Periodical Title): ISSN : 1613-4125
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2023-03-15
• Dissertation Number: 甲第861号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Angiotensin-II; BCAA; liver cirrhosis; muscle atrophy; myokine
• Target Audience: 一般
• Note (General): type:Thesis; Scope: This study investigated the combined effect of the angiotensin II (AT-II) receptor blocker losartan and branched-chain amino acids (BCAAs) on skeletal muscle atrophy in rats with cirrhosis and steatohepatitis. Method and Results: Fischer 344 rats are fed a choline-deficient l-amino acid-defined (CDAA) diet for 12 weeks and treated with oral losartan (30 mg kg−1 day−1) and/or BCAAs (Aminoleban EN, 2500 mg kg−1 day−1). Treatment with losartan and BCAAs attenuated hepatic inflammation and fibrosis and improved skeletal muscle atrophy and strength in CDAA-fed rats. Both agents reduced intramuscular myostatin and pro-inflammatory cytokine levels, resulting in inhibition of the ubiquitin–proteasome system (UPS) through interference with the SMAD and nuclear factor-kappa B pathways, respectively. Losartan also augmented the BCAA-mediated increase of skeletal muscle mass by promoting insulin growth factor-I production and mitochondrial biogenesis. Moreover, losartan decreased the intramuscular expression of transcription factor EB (TFEB), a transcriptional inducer of E3 ubiquitin ligase regulated by AT-II. In vitro assays illustrated that losartan promoted mitochondrial biogenesis and reduced TFEB expression in AT-II-stimulated rat myocytes, thereby potentiating the inhibitory effects of BCAAs on the UPS and caspase-3 cleavage. Conclusion: These results indicate that this regimen could serve as a novel treatment for patients with sarcopenia and liver cirrhosis.; 博士（医学）・甲第861号・令和5年3月15日; This is the peer reviewed version of the following article: [Soichi, Takeda et al. Angiotensin Receptor Blockers Potentiate the Protective Effect of Branched-Chain Amino Acids on Skeletal Muscle Atrophy in Cirrhotic Rats. Molecular Nutrition & Food Research. 2021, 65(24), 2100526.], which has been published in final form at [https://doi.org/10.1002/mnfr.202100526]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.; identifier:Molecular nutrition & food research.,Vol.65 No.24 Article No.e2100526 (2021 Dec); identifier:16134125; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4092; identifier:Molecular nutrition & food research., 65(24): e2100526
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4092/1/01%e7%94%b2861%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4092/2/02%e7%94%b2861%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4092/6/03%e7%94%b2861%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1002/mnfr.202100526
• Periodical Title (NCID): AA12809751; https://ci.nii.ac.jp/ncid/AA12809751
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU