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Leucine and ω‐3 fatty acids act synergistically through mTOR to activate translation initiation in young and aged C2C12 myotubes (820.18)
Author(s) -
Baum Jamie,
Shouse Stepanie,
Wei Jeanne,
Wolfe Robert
Publication year - 2014
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.28.1_supplement.820.18
Subject(s) - myogenesis , skeletal muscle , pi3k/akt/mtor pathway , mtorc1 , mechanistic target of rapamycin , c2c12 , leucine , medicine , myocyte , endocrinology , phosphorylation , chemistry , biology , biochemistry , signal transduction , amino acid
Skeletal muscle is a major site of metabolic activity. For skeletal muscle to function at optimal levels, activation of processes that regulate muscle development, growth, and metabolism is required. Nutrition is an important modulator of health and function in aging and it is important to develop an optimal nutritional therapy that will improve skeletal muscle function in aging. Leu and ω−3 FA (EPA/DHA) are ideal candidates. The objective of this study was to determine if treatment with leu+ω−3 FA improves skeletal muscle function in aged cells through an mTOR‐mediated pathway. Young and aged C2C12 myotubes were serum and leu starved for 6 hr followed by treatment with rapamycin or DMSO for 1 hr. Cells then received one of four physiological treatments: control, 0.5mM leu, 60μM EPA/240μM DHA, or leu+EPA/DHA for 60 min. Both leu and ω−3 FA increased signaling through mTOR by hyperphosphorylating p70S6K and 4EBP1 (p<0.05) in young and aged cells, however aged cells were less responsive to nutrient treatment. Leu+ω−3 FA had a synergistic effect (p<0.05) on p70S6K and 4EBP1 phosphorylation. Treatment with rapamycin blunted the nutrient response, suggesting leu and ω−3 FA act via mTOR to regulate muscle function. Taken together, these data suggest that leu and ω−3 FA are potential candidates for nutrition therapy during aging. Grant Funding Source : Supported by UAMS Pepper Center Pilot Grant AG028718.