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Measuring Skeletal Muscle Thermogenesis in Mice and Rats
Published on: July 27, 2022
Hyperthermia increases interleukin-6 in mouse skeletal muscle
Steven S Welc1, Neil A Phillips, Jose Oca-Cossio
1Department of Applied Physiology & Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, USA.
American Journal of Physiology. Cell Physiology
|June 8, 2012
Summary
Skeletal muscle responds to heat stress by increasing interleukin-6 (IL-6) production. This heat-induced muscle IL-6 response is mediated by heat shock proteins and occurs independently of exercise.
Area of Science:
- Exercise Physiology
- Molecular Biology
- Muscle Biology
Background:
- Skeletal muscles release interleukin-6 (IL-6) during exercise, influencing systemic inflammation.
- The IL-6 response from muscle is diminished when core body temperature decreases.
- This suggests hyperthermia, or elevated body temperature, may independently stimulate muscle IL-6.
Purpose of the Study:
- To investigate if hyperthermia is an independent stimulus for interleukin-6 (IL-6) production in skeletal muscle.
- To explore the role of heat shock proteins in mediating this response.
- To examine the impact of hyperthermia on tumor necrosis factor-alpha (TNF-α) gene expression in muscle.
Main Methods:
- Cultured C2C12 myotubes and myoblasts were exposed to varying temperatures (41°C and 42°C).
- Isolated mouse soleus muscles were subjected to ex vivo hyperthermia (41°C).
- Intact mice were exposed to passive hyperthermia (core temperature reaching 42.4°C).
- Gene expression of IL-6, TNF-α, and HSP72 was measured using quantitative PCR.
- Pharmacological inhibition of heat shock factor was employed using KNK437.
Main Results:
- Hyperthermia (42°C) significantly increased IL-6 gene expression and protein secretion in cultured myotubes.
- Exposure to 41°C induced a moderate increase in IL-6 mRNA in isolated soleus muscles and in vivo.
- Tumor necrosis factor-alpha (TNF-α) gene expression was suppressed by hyperthermia in isolated models but elevated in vivo.
- Muscle HSP72 mRNA levels increased with hyperthermia, and IL-6 mRNA elevation was proportional to HSP72.
- Blocking heat shock factor suppressed heat-induced increases in both HSP72 and IL-6 mRNA.
Conclusions:
- Skeletal muscle acts as a heat stress sensor, responding to physiologically relevant hyperthermia.
- Hyperthermia independently stimulates muscle IL-6 production, a response mediated by heat shock factor and HSP72.
- Muscle exhibits a programmed cytokine response to heat stress, characterized by elevated IL-6 and modulated TNF-α.
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