Isometric Contraction Attenuates Leucine-Stimulated 4E-Binding Protein 1 Phosphorylation in Contralateral Noncontracted Skeletal Muscle in Mice.

BACKGROUND: Skeletal muscle contraction can influence anabolic signaling in distant noncontracted muscle. However, whether unilateral contraction alters nutrient-stimulated mechanistic target of rapamycin complex 1 (mTORC1) signaling in contralateral muscle remains unclear.

OBJECTIVES: This study aimed to determine whether unilateral isometric contraction attenuates leucine-stimulated mTORC1 signaling and protein synthesis in contralateral noncontracted muscle in mice.

METHODS: Ten-wk-old male C57BL/6J mice fed a standard chow diet (CE-2) were assigned to resting or unilateral isometric contraction conditions and received water or leucine (1.35 g/kg body weight) 2 h after contraction (n = 8/group). Gastrocnemius muscles were collected 3 h postcontraction. Regulated in development and DNA damage responses 1 (REDD1) protein abundance, mTORC1 signaling, protein synthesis, and serum branched-chain amino acid (BCAA) concentrations were measured. Data were analyzed using 2-way analysis of variance (ANOVA) followed by Holm-adjusted post hoc tests.

RESULTS: Unilateral contraction increased REDD1 protein abundance in contralateral noncontracted muscle, with a significant interaction between leucine and contraction (P = 0.0499). REDD1 protein abundance was higher in the isometric contraction groups than in the resting groups under water and leucine conditions. Two-way ANOVA revealed a significant interaction between leucine and contraction for 4E-binding protein 1 (4E-BP1) phosphorylation (P = 0.046). Under resting conditions, leucine increased 4E-BP1 phosphorylation compared with water, whereas this response was attenuated under contraction conditions. Ribosomal protein S6 kinase 1 phosphorylation was unchanged. Protein synthesis was increased by leucine (main effect, P < 0.001) and reduced by contraction (main effect, P < 0.001), with no significant interaction. Serum BCAA concentrations were increased by leucine (main effect, P < 0.001), with no effect of contraction or interaction.

CONCLUSIONS: In male C57BL/6J mice, unilateral isometric contraction attenuated leucine-stimulated 4E-BP1 phosphorylation in contralateral noncontracted skeletal muscle. Protein synthesis was reduced by contraction independently of leucine treatment. These effects occurred without differences in circulating BCAA availability, suggesting altered anabolic signaling responsiveness to nutritional stimulation.