The Lab

With a steadily rising number of incidences, obesity has become the leading medical disorder of the 21th century. Moreover, it is associated with conditions such as insulin resistance and type 2 diabetes. About 200 million people worldwide already suffer from type 2 diabetes and the prediction is that this number will rise to 366 million by the year 2030. Being responsible for 70% of total body glucose disposal, muscle represents a critical organ in the development of insulin resistance. Indeed, muscle activity – exercise – protects against obesity and insulin resistance, and the development of so-called exercise mimetics has therefore been proposed as a novel therapeutic strategy.  But this has failed so far because we still do not completely understand the etiology of glucose intolerance and how exercise improves glucose tolerance. In particular, angiogenesis – the growth of new blood vessels from existing ones – is an early adaptive event following exercise training, but the role of the muscle vasculature in the regulation of muscle metabolism and glucose tolerance has been largely overlooked.

Glucose, but also oxygen and other nutrients, are delivered to the muscle via an ingenuous network of blood vessels that are aligned by endothelial cells (ECs). To meet the increased metabolic demand of the exercising muscle, the formation of new vessels from pre-existing ones, a highly dynamic and tightly controlled process termed angiogenesis, is promoted. However, it is not yet known how muscle metabolism following exercise coordinates the formation of new blood vessels and whether muscle angiogenesis can affect the development of obesity and insulin resistance. Interestingly, it was recently described that endothelial metabolism also drives angiogenesis as genetic knockdown of the glycolytic regulator PFKFB3 impaired physiological angiogenesis in the postnatal retina (De Bock et al., Cell 2013) suggesting that endothelial metabolism might also contribute to exercise mediated blood vessel growth or muscle insulin sensitivity. The Laboratory of Exercise and Health will therefore unravel the crosstalk between the triad exercise – angiogenesis – metabolism in the regulation of muscle homeostasis (insulin sensitivity, muscle mass). We will use a translational approach from cells via mice to humans to elucidate the molecular mechanisms behind this metabolic crosstalk.