Pharmacological and genetic approaches to modulate energy metabolism in skeletal muscle cells

Abstract

The prevalence of obesity and related metabolic illnesses have rapidly increased over the last decades. One of these diseases is type 2 diabetes (T2D), characterized by chronic hyperglycaemia and insulin resistance in several organs including skeletal muscle, an organ of particular interest when it comes to further understand metabolic conditions. In this thesis, we aimed to study the effects of different pharmacological and genetic approaches on skeletal muscle energy metabolism. The results presented in this thesis shows that activation of β2-adrenergic receptors and the cold-sensing transient receptor potential ion channels (TRP), inhibiting diacylglycerol acyltransferase (DGAT) and ablation of the α2 subunit of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) affected energy metabolism in myotubes. The β2- agonist terbutaline increased glucose uptake, glucose and fatty acid oxidation, upregulated mitochondrial and oxidative pathways and increased protein synthesis. Activation of TRPA1 resulted in an increased glucose uptake and oxidation, whereas inhibiting of DGAT and ablation of α2 subunit of AMPK resulted in alterations in lipid metabolism.