Muscular interleukin-6 differentially regulates skeletal muscle adaptation to high-fat diet in a sex-dependent manner

- Muscle interleukin-6 (IL-6) influences skeletal muscle sex-dependently.
- Muscle IL-6 regulates fiber-size gain induced by a high-fat diet (HFD) in males.
- Muscle IL-6 regulates fiber-type switching induced by a high-fat diet (HFD) in females.
- Muscle IL-6 regulates collagen deposition by HFD depending on sex and muscle type.

Interleukin-6 (IL-6) is now known to be not only a major cytokine controlling the immune system but also basic physiological variables such as body weight and metabolism. We recently reported that muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner in mice. When compared with littermate floxed controls, males gained less weight whereas females gained more weight after a 12-week high-fat diet treatment (HFD). We herewith report gender-differences of HFD treatment on fast and slow skeletal muscle in muscle-specific IL-6 deficient mice. While gross muscle architecture was normal, in males, HFD resulted in an increased proportion of medium-large size myofibers which was prevented by muscle IL-6 deletion. No modifications of fiber size were observed in females. HFD induced a fiber-type switching in tibialis muscle, increasing the proportion of fast-oxidative fibers and decreasing the fast-glycolytic fibers in female mice which were dependent on muscle IL-6. No changes of fiber types were detected in males. Finally, HFD was associated with increased collagen deposition in both sexes and muscle types. However, this effect was only associated to the presence of muscular IL-6 only on the slow soleus muscle in males. The results demonstrate sex-dependent effects of both HFD and muscle IL-6 deficiency in skeletal muscle.