Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

Ishikawa, Takuya; Kitaura, Yasuyuki; Kadota, Yoshihiro; Morishita, Yukako; Ota, Miki; Yamanaka, Fumiya; Xu, Minjun; Ikawa, Masahito; Inoue, Naokazu; Kawano, Fuminori; Nakai, Naoya; Murakami, Taro; Miura, Shinji; Hatazawa, Yukino; Kamei, Yasutomi; Shimomura, Yoshiharu

doi:https://doi.org/10.1038/srep39825

Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

Ishikawa, Takuya; Kitaura, Yasuyuki; Kadota, Yoshihiro et al.

Scientific Reports, 2017, 7, 39825

アクセス数:250件（2025-04-18 02:44 集計）

固定URL: https://hdl.handle.net/11094/78583

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タイトル	Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition
著者	NRID 1000000792649 1000000792649 著者名 Ishikawa, Takuya
	NRID 1000090442954 1000090442954 著者名 Kitaura, Yasuyuki
	NRID 1000010724776 1000010724776 著者名 Kadota, Yoshihiro
	著者名 Morishita, Yukako
	著者名 Ota, Miki
	著者名 Yamanaka, Fumiya
	著者名 Xu, Minjun
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 著者名 Ikawa, Masahito
	NRID 1000050379096 1000050379096 著者名 Inoue, Naokazu
	NRID 1000090346156 1000090346156 著者名 Kawano, Fuminori
	NRID 1000090324508 1000090324508 著者名 Nakai, Naoya
	NRID 1000010252305 1000010252305 著者名 Murakami, Taro
	NRID 1000010342932 1000010342932 著者名 Miura, Shinji
	著者名 Hatazawa, Yukino
	NRID 1000070300829 1000070300829 著者名 Kamei, Yasutomi
	NRID 1000030162738 1000030162738 著者名 Shimomura, Yoshiharu
内容	Ishikawa, T., Kitaura, Y., Kadota, Y. et al. Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. Sci Rep 7, 39825 (2017). https://doi.org/10.1038/srep39825
抄録	Branched-chain amino acids (BCAAs) are essential amino acids for mammals and play key roles in the regulation of protein metabolism. However, the effect of BCAA deficiency on protein metabolism in skeletal muscle in vivo remains unclear. Here we generated mice with lower BCAA concentrations by specifically accelerating BCAA catabolism in skeletal muscle and heart (BDK-mKO mice). The mice appeared to be healthy without any obvious defects when fed a protein-rich diet; however, bolus ingestion of BCAAs showed that mTORC1 sensitivity in skeletal muscle was enhanced in BDK-mKO mice compared to the corresponding control mice. When these mice were fed a low protein diet, the concentration of myofibrillar protein was significantly decreased (but not soluble protein) and mTORC1 activity was reduced without significant change in autophagy. BCAA supplementation in drinking water attenuated the decreases in myofibrillar protein levels and mTORC1 activity. These results suggest that BCAAs are essential for maintaining myofibrillar proteins during protein undernutrition by keeping mTORC1 activity rather than by inhibiting autophagy and translation. This is the first report to reveal the importance of BCAAs for protein metabolism of skeletal muscle in vivo.
出版者	Nature Research
収録物名	Scientific Reports
巻(号)	7
ページ	39825
刊行年月	2017-01-04
言語	英語
ハンドルURL	https://hdl.handle.net/11094/78583
eISSN	20452322
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/srep39825
関連情報 (isIdenticalTo)	PMID 28051178
アクセス権	open access
権利情報	© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Scientific Reports. 2017, 7, p. 39825
DC.title	Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition
DC.creator	Ishikawa, Takuya
	Kitaura, Yasuyuki
	Kadota, Yoshihiro
	Morishita, Yukako
	Ota, Miki
	Yamanaka, Fumiya
	Xu, Minjun
	Ikawa, Masahito
	Inoue, Naokazu
	Kawano, Fuminori
	Nakai, Naoya
	Murakami, Taro
	Miura, Shinji
	Hatazawa, Yukino
	Kamei, Yasutomi
	Shimomura, Yoshiharu
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2017-01-04
DC.identifier	https://doi.org/10.1038/srep39825
DC.description	Ishikawa, T., Kitaura, Y., Kadota, Y. et al. Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. Sci Rep 7, 39825 (2017). https://doi.org/10.1038/srep39825
DCTERMS.abstract	Branched-chain amino acids (BCAAs) are essential amino acids for mammals and play key roles in the regulation of protein metabolism. However, the effect of BCAA deficiency on protein metabolism in skeletal muscle in vivo remains unclear. Here we generated mice with lower BCAA concentrations by specifically accelerating BCAA catabolism in skeletal muscle and heart (BDK-mKO mice). The mice appeared to be healthy without any obvious defects when fed a protein-rich diet; however, bolus ingestion of BCAAs showed that mTORC1 sensitivity in skeletal muscle was enhanced in BDK-mKO mice compared to the corresponding control mice. When these mice were fed a low protein diet, the concentration of myofibrillar protein was significantly decreased (but not soluble protein) and mTORC1 activity was reduced without significant change in autophagy. BCAA supplementation in drinking water attenuated the decreases in myofibrillar protein levels and mTORC1 activity. These results suggest that BCAAs are essential for maintaining myofibrillar proteins during protein undernutrition by keeping mTORC1 activity rather than by inhibiting autophagy and translation. This is the first report to reveal the importance of BCAAs for protein metabolism of skeletal muscle in vivo.
DC.rights	© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78583
citation_title	Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition
citation_author	Ishikawa, Takuya
	Kitaura, Yasuyuki
	Kadota, Yoshihiro
	Morishita, Yukako
	Ota, Miki
	Yamanaka, Fumiya
	Xu, Minjun
	Ikawa, Masahito
	Inoue, Naokazu
	Kawano, Fuminori
	Nakai, Naoya
	Murakami, Taro
	Miura, Shinji
	Hatazawa, Yukino
	Kamei, Yasutomi
	Shimomura, Yoshiharu
citation_publisher	Nature Research
citation_language	英語
citation_date	2017-01-04
citation_journal_title	Scientific Reports
citation_volume	7
citation_firstpage	39825
citation_doi	https://doi.org/10.1038/srep39825
citation_pmid	28051178
citation_public_url	https://hdl.handle.net/11094/78583

Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

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