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Endurance Capacity of Muscle‐specific Branched‐chain alpha‐Ketoacid Dehydrogenase (BCKDH) Kinase‐deficient Mice
Author(s) -
Shimomura Yoshiharu,
Xu Minjun,
Ishikawa Takuya,
Kadota Yoshihiro,
Morioka Takashi,
Toyoda Takanari,
Kato Rina,
Kondo Yusuke,
Ota Miki,
Morishita Yukako,
Bariuan Jussiaea,
Zhen Hongmin,
Kitaura Yasuyuki
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.129.4
Subject(s) - catabolism , valine , medicine , endocrinology , alkaline phosphatase , leucine , chemistry , phosphorylation , isoleucine , biochemistry , amino acid , enzyme , metabolism
The main catabolic pathway of branched‐chain amino acids (BCAAs: leucine, isoleucine, and valine) is located in mitochondria. The rate‐limiting step of the catabolism in muscle tissues is catalyzed by BCKDH complex, which is located at the second step in the pathway. The activity of BCKDH complex is regulated by covalent modification, and BCKDH kinase (BDK) is responsible for inactivation of the complex by phosphorylation. In the present study, we produced muscle‐specific BDK knockout (BDK‐mKO) mice. The muscle BCAA concentrations were less than half in BDK‐mKO mice than in control mice. We assessed the endurance capacity of BDK‐mKO mice and control mice at 12 weeks of age (under untrained conditions) and at 21 weeks of age after 9 weeks training by measuring the distance of running to exhaustion using treadmill with 10% grade. The running speed in the test was initial 15 m/min for 4 min and then increased at the rate of 1 m/min every 4 min. The training was performed 5 days/week by running for 60 min/day at the speed of 15 m/min in the initial 4 weeks and 18 m/min in the following 5 weeks. The endurance capacity in control mice was 633 ± 109 m (mean ± SE, n=8) before training and 1,529 ± 165 m after training, and that in BDK‐mKO mice was 1,020 ± 45 m and 1,004 ± 110 m, respectively. These results indicate that BDK‐mKO mice, in contrast to control mice, did not adapt to the endurance training, suggesting that BCAAs play an important role in adaptation to exercise training.