Branched-chain amino acids (BCAAs) are essential for muscle protein synthesis and are widely acknowledged for mitigating sarcopenia. Oligonol (R) (Olg), a low-molecular-weight polyphenol from Litchi chinensis, has also been found to attenuate sarcopenia by improving mitochondrial quality and positive protein turnover. This study aims to investigate the effect of Olg on BCAA-stimulated protein synthesis in sarcopenia. In sarcopenic C57BL/6 mice and senescence-accelerated mouse-prone 8 (SAMP8) mice, BCAAs were significantly decreased in skeletal muscle but increased in blood serum. Furthermore, the expressions of membrane L-type amino acid transporter 1 (LAT1) and branched-chain amino acid transaminase 2 (BCAT2) in skeletal muscle were lower in aged mice than in young mice. The administration of Olg for 8 weeks significantly increased the expressions of membrane LAT1 and BCAT2 in the skeletal muscle when compared with non-treated SAMP8 mice. We further found that BCAA deprivation via LAT1-siRNA in C2C12 myotubes inhibited the signaling of protein synthesis and facilitated ubiquitination degradation of BCAT2. In C2C12 cells mimicking sarcopenia, Olg combined with BCAA supplementation enhanced mTOR/p70S6K activity more than BCAA alone. However, blocked LAT1 by JPH203 reversed the synergistic effect of the combination of Olg and BCAAs. Taken together, changes in LAT1 and BCAT2 during aging profoundly alter BCAA availability and nutrient signaling in aged mice. Olg increases BCAA-stimulated protein synthesis via modulating BCAA transportation and BCAA catabolism. Combining Olg and BCAAs may be a useful nutritional strategy for alleviating sarcopenia.
机构:
Hannover Med Sch, Inst Clin Pharmacol, Hannover, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
Haufe, S.
Engeli, S.
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Hannover Med Sch, Inst Clin Pharmacol, Hannover, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
Engeli, S.
Kaminski, J.
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机构:
Charite, Med Sch, Expt & Clin Res Ctr, Franz Volhard Clin Res Ctr, Berlin, Germany
Max Delbruck Ctr Mol Med, Berlin, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
机构:
Charite, Med Sch, Expt & Clin Res Ctr, Franz Volhard Clin Res Ctr, Berlin, Germany
Max Delbruck Ctr Mol Med, Berlin, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
Haas, V.
Maehler, A.
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Charite, Med Sch, Expt & Clin Res Ctr, Franz Volhard Clin Res Ctr, Berlin, Germany
Max Delbruck Ctr Mol Med, Berlin, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
Maehler, A.
Schulz-Menger, J.
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HELIOS Klinikum Berlin Buch, Clin Cardiol & Nephrol, Working Grp Cardiac MRI, Berlin, Germany
Univ Med Berlin, Expt & Clin Res Ctr, Charite Campus Buch, Berlin, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
Schulz-Menger, J.
Luft, F. C.
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Charite, Med Sch, Expt & Clin Res Ctr, Franz Volhard Clin Res Ctr, Berlin, Germany
Max Delbruck Ctr Mol Med, Berlin, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
Luft, F. C.
Boschmann, M.
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Charite, Med Sch, Expt & Clin Res Ctr, Franz Volhard Clin Res Ctr, Berlin, Germany
Max Delbruck Ctr Mol Med, Berlin, GermanyHannover Med Sch, Inst Clin Pharmacol, Hannover, Germany
机构:
Staffordshire Univ, Sport & Exercise Sci, Brindley Bldg,Leek Rd, Stoke On Trent, Staffs, EnglandSt Marys Univ, Sch Sport Hlth & Appl Sci, Waldegrave Rd, London TW1 4SX, England
Burt, Dean
Howe, Louis
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St Marys Univ, Sch Sport Hlth & Appl Sci, Waldegrave Rd, London TW1 4SX, EnglandSt Marys Univ, Sch Sport Hlth & Appl Sci, Waldegrave Rd, London TW1 4SX, England
Howe, Louis
Patterson, Stephen David
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St Marys Univ, Sch Sport Hlth & Appl Sci, Waldegrave Rd, London TW1 4SX, EnglandSt Marys Univ, Sch Sport Hlth & Appl Sci, Waldegrave Rd, London TW1 4SX, England
机构:
Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Fuji City Gen Hosp, Dept Internal Med, Div Gastroenterol, 50 Takashima Cho, Fuji, Shizuoka 4178567, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Saeki, Chisato
Kanai, Tomoya
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Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Fuji City Gen Hosp, Dept Internal Med, Div Gastroenterol, 50 Takashima Cho, Fuji, Shizuoka 4178567, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Kanai, Tomoya
Nakano, Masanori
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Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Fuji City Gen Hosp, Dept Internal Med, Div Gastroenterol, 50 Takashima Cho, Fuji, Shizuoka 4178567, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Nakano, Masanori
Oikawa, Tsunekazu
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Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Oikawa, Tsunekazu
Torisu, Yuichi
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Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Fuji City Gen Hosp, Dept Internal Med, Div Gastroenterol, 50 Takashima Cho, Fuji, Shizuoka 4178567, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Torisu, Yuichi
Saruta, Masayuki
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Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan
Saruta, Masayuki
Tsubota, Akihito
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Jikei Univ, Sch Med, Res Ctr Med Sci, Core Res Facil,Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, JapanJikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan