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Updated: Jun 5, 2026

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
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Isometric Contraction Attenuates Leucine-Stimulated 4E-Binding Protein 1 Phosphorylation in Contralateral

Yuzuki Ando1, Taro Murakami1

  • 1Department of Nutrition, Shigakkan University, Obu, Aichi, Japan.

The Journal of Nutrition
|June 3, 2026
PubMed
Abstract

Insights

Unilateral muscle contraction reduces the anabolic signaling response to leucine in the contralateral leg. This suggests that exercise can blunt nutrient-driven muscle growth signals, even in non-exercised muscles.

Area of Science:

  • Exercise Physiology
  • Molecular Biology
  • Nutritional Biochemistry

Background:

  • Skeletal muscle contraction can induce anabolic signaling in non-contracted muscles.
  • The effect of unilateral contraction on nutrient-stimulated mTORC1 signaling in contralateral muscle is not well understood.

Purpose of the Study:

  • To investigate if unilateral isometric contraction attenuates leucine-stimulated mechanistic target of rapamycin complex 1 (mTORC1) signaling and protein synthesis in contralateral non-contracted mouse skeletal muscle.

Main Methods:

  • Male C57BL/6J mice underwent unilateral isometric contraction or rest.
  • Mice received water or leucine (1.35 g/kg) post-contraction.
  • Contralateral gastrocnemius muscles were analyzed for REDD1, mTORC1 signaling (4E-BP1, S6K1 phosphorylation), and protein synthesis.
  • Serum branched-chain amino acid (BCAA) concentrations were measured.

Main Results:

  • Unilateral contraction increased REDD1 protein abundance in contralateral muscle.
  • Leucine increased 4E-BP1 phosphorylation under resting conditions, but this was attenuated by contraction.
  • Protein synthesis was reduced by contraction independently of leucine.
  • Serum BCAA concentrations were increased by leucine but unaffected by contraction.

Conclusions:

  • Unilateral isometric contraction attenuates leucine-stimulated 4E-BP1 phosphorylation in contralateral skeletal muscle.
  • Contraction reduced protein synthesis irrespective of leucine availability.
  • Altered anabolic signaling responsiveness to nutrients may occur without changes in circulating BCAA levels.
Keywords:
Rag GTPaseRhebamino acid sensinganabolic resistanceintermuscular communication

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