[Low temperature exposure increases IL-6 expression in skeletal muscle cells]

Area of Science:

• Physiology
• Cell Biology
• Molecular Biology

Background:

• Shivering and nonshivering thermogenesis in skeletal muscles are crucial for maintaining body temperature.
• Adipose tissue responds to cold autonomously, but skeletal muscle's direct cold response is unknown.
• Transient receptor potential (TRP) channels like TRPM8 and TRPA1 are key cold sensors.

Purpose of the Study:

• To investigate if skeletal muscle cells can directly respond to low temperatures in an autoregulatory manner.
• To identify molecular mechanisms underlying skeletal muscle's response to cold.
• To explore the role of TRP channels in skeletal muscle cold sensing.

Main Methods:

• RT-PCR was used to detect TRPM8 expression in mouse skeletal muscle and C2C12 myotubes.
• RNA-sequencing analyzed gene expression changes in C2C12 myotubes after cold exposure (33°C for 6h).
• KEGG-Pathway and protein-protein interaction network analyses identified key signaling pathways and genes.

Main Results:

• TRPM8 was expressed in mouse skeletal muscle and C2C12 myotubes.
• Low temperature significantly altered gene expression patterns in C2C12 myotubes, affecting pathways like IL-17, TNFα, MAPK, and Wnt.
• Interleukin-6 (IL-6) was identified as a key gene upregulated by cold, with both mRNA and protein levels increasing.

Conclusions:

• Skeletal muscle cells possess a direct autoregulatory response to low temperatures.
• This response is characterized by the upregulation of Interleukin-6 (IL-6) expression.
• The findings highlight a novel cellular mechanism for thermogenesis in skeletal muscle.