Lærke Bertholdt - Role of muscle IL-6 in substrate recruitment during exercise and fasting: impact of T2D

Type 2 diabetes (T2D) is associated with metabolic inflexibility during not only food intake, but also during exercise. Furthermore, substrate recruitment from adipose tissue and liver is essential during challenges like exercise and fasting. However, knowledge of the underlying mechanisms behind exercise- and fasting-induced regulation of liver and adipose tissue metabolism and substrate recruitment during metabolic challenges as well as the alterations with T2D is limited.

Muscle-derived interleukin 6 (IL-6) is released from contracting skeletal muscle and has been suggested to regulate substrate recruitment from liver and adipose tissue during exercise. Furthermore IL-6 has been suggested also to play a role during fasting.

Therefore the overall aim of this project is to elucidate the role of muscle IL-6 in substrate recruitment from liver and adipose tissue during exercise and fasting and the impact of T2D.

This will be addressed by the use of IL-6 muscle specific knockout (MKO) mice, an inducible IL-6 MKO mouse strain, human studies with young men and type 2 diabetic patients as well as hepatocyte cell cultures. Thus, the project seeks to elucidate the understanding of T2D during metabolic challenges present during fasting and exercise and with focus on IL-6-mediated crosstalk from skeletal muscle to liver and adipose tissue.