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Nutrient signaling in the regulation of human muscle protein synthesis
Author(s) -
Fujita Satoshi,
Dreyer Hans C,
Drummond Micah J,
Glynn Erin L,
Cadenas Jerson G,
Yoshizawa Fumiaki,
Volpi Elena,
Rasmussen Blake B
Publication year - 2007
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.21.5.a713-c
Subject(s) - pi3k/akt/mtor pathway , p70 s6 kinase 1 , ampk , anabolism , phosphorylation , protein kinase b , rptor , signal transduction , mtorc1 , chemistry , mtorc2 , medicine , endocrinology , microbiology and biotechnology , biochemistry , biology , protein kinase a
AMPK and mTOR are important energy and nutrient sensing and signaling proteins in muscle. AMPK activation decreases muscle protein synthesis (MPS) by inhibiting mTOR signaling. Essential amino acids and insulin stimulate mTOR signaling and MPS. We hypothesized that anabolic nutrients would be sensed by both AMPK and mTOR resulting in an acute and potent stimulation of MPS via enhanced translation initiation and elongation. We measured MPS and mTOR‐associated upstream and downstream signaling proteins in young subjects using stable isotopic and immunoblotting techniques. Following a 1st muscle biopsy from the vastus lateralis, subjects ingested a nutrient mixture (EAC) containing essential amino acids (0.35 grams/kg LM) and carbohydrate (0.5 grams/kg LM). Total caloric content was 186.9 ± 8 kcal. A 2nd biopsy was obtained 1 hr later. Ingestion of EAC significantly increased MPS, Akt/PKB, and mTOR phosphorylation (P<0.05) while modestly reducing AMPK phosphorylation. mTOR signaling to its downstream effectors (S6K1 and 4E‐BP1 phosphorylation status) was increased to a large extent (P<0.05). In addition, eEF2 phosphorylation was significantly reduced (P<0.05). We conclude that anabolic nutrients are sensed primarily by the mTOR nutrient signaling pathway in human muscle which increases MPS not only via enhanced translation initiation but also through signaling promoting translation elongation. Support: NIH R01 AR049877 and NIH P30 AG17231