Acute Cold Exposure Cell-Autonomously Reduces mTORC1 Signaling and Protein Synthesis Independent of AMPK

Area of Science:

• Skeletal Muscle Physiology
• Cellular Metabolism
• Cryotherapy Research

Background:

• Cryotherapy is widely used for muscle recovery, but its effectiveness remains debated.
• Understanding the precise cellular mechanisms of cold exposure on muscle is crucial for optimizing its application.

Purpose of the Study:

• To investigate the cell-autonomous effects of acute cold exposure on mouse myoblasts.
• To elucidate the role of the AMPK/mTORC1 signaling pathway in mediating these effects.
• To determine if cold-induced metabolic changes in myoblasts are dependent on AMPK activation.

Main Methods:

• Primary mouse myoblasts (wild-type and AMPK double-knockout) were subjected to cold (26 °C) or standard (37 °C) conditions.
• Assessed myoblast proliferation, differentiation, protein synthesis, and mTORC1 pathway activity.
• Evaluated the impact of cold exposure on myotube characteristics like size and fusion index.

Main Results:

• Cold exposure activated AMPK and decreased mTORC1 activity and protein synthesis.
• Inhibition of mTORC1 and protein synthesis by cold occurred independently of AMPK.
• Cold exposure suppressed myoblast proliferation in wild-type but not AMPK-deficient cells.
• Cold did not affect myotube size, but AMPK-deficient myotubes showed altered fusion and size.

Conclusions:

• Cold-induced AMPK activation contributes to reduced myoblast proliferation.
• AMPK is not essential for cold-induced suppression of the mTORC1 pathway and protein synthesis.
• These findings provide novel insights into the cell-autonomous metabolic responses of skeletal muscle to cryotherapy.