Physical inactivity is recognized as one of the main causes of the development of metabolic disorders. Lack of exercise and a sedentary lifestyle have been linked to the onset of type 2 diabetes (T2D) and insulin resistance. Conversely, the benefits of physical exercise for the prevention and treatment of diabetes and its complications are well-documented. Despite the growing number of treatments available for T2D, physical exercise remains a first-line intervention strategy due to its effectiveness. However, the molecular mechanisms underlying the beneficial effects of physical activity are numerous and complex.

The contractile activity of skeletal muscle enhances its ability to secrete mediators, known as myokines, which may explain the positive effects of physical activity on chronic diseases by influencing distant tissues. Some myokines act locally via paracrine mechanisms, exerting their effects on intramuscular signaling pathways. Other myokines are thought to act as hormones, exerting specific endocrine effects on other organs, such as the liver and adipose tissue.

Understanding how organs communicate through secreted factors has become an innovative avenue of research. Physical exercise is associated with metabolic changes in skeletal muscle, notably through the activation of AMPK (AMP-activated protein kinase), a key regulator of energy metabolism. Our objective is to identify new myokines secreted by skeletal muscle in response to pharmacological activation of AMPK, a crucial player in the adaptation of skeletal muscle to exercise. We aim to answer the following questions:

1. Which myokines have their expression and secretion stimulated by muscle AMPK activation?
2. Can we identify the myokines involved in the crosstalk between skeletal muscle and the liver?
3. What are the effects of these myokines on hepatic metabolism?