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LAT1 muscle‐specific knockout limits early load‐induced mTORC1 activity (1102.41)
Author(s) -
Aguirre Nicholas,
Baar Keith
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.1102.41
Subject(s) - anabolism , mtorc1 , chemistry , leucine , skeletal muscle , medicine , biochemistry , signal transduction , amino acid , pi3k/akt/mtor pathway
Leucine exhibits a strong anabolic effect in skeletal muscle: increasing muscle protein synthesis via activation of mechanistic target of rapamycin‐complex 1 (mTORC1). Since LAT1 is the primary leucine transporter in skeletal muscle, its regulation could affect anabolic resistance. The purpose of this study was to elucidate the role of LAT1 muscle‐specific knockout (mKO) on mTORC1 activity after acute loading. Three month old control (CON; n = 11) and LAT1 mKO mice (mKO; n = 12) were anesthetized and unilaterally loaded. Tibialis anterior muscles were collected bilaterally 30 min, 3 h and 18 h post‐loading and mTORC1 activity was determined using western blot analysis of phospho/total S6K1 389 (pS6K1). pS6K1 increased 30 min and 3 h post‐loading from non‐stimulated limbs (NS) to stimulated limbs (S) for CON (30 min: NS: 0.98 ± 0.11, S: 3.46 ± 0.36, p < 0.01; 3 h: NS: 0.98 ± 0.23, S: 9.95 ± 1.58, p < 0.01) and mKO (30 min: NS: 1.16 ± 0.13, S: 1.74 ± 0.52, p = 0.27; 3 h: NS: 1.08 ± 0.14, S: 7.75 ± 1.99, p < 0.01). Stimulated pS6K1 was higher in CON than mKO at 30 min (p < 0.05) post‐loading. We conclude LAT1 mKO limits early mTORC1 activation and might contribute to anabolic resistance post‐loading.