Nutrient regulation of energy metabolism in relation to obesity and type 2 diabetes
Year: 2010
Type: dissertation
Abstract: Over the past decades many western countries have witnessed an epidemic rise in obesity, insulin resistance and type 2 diabetes. There clearly is a link between increased fat storage and decreased insulin sensitivity leading to type 2 diabetes, but the mechanistic explanations have been difficult to pinpoint biochemically and genetically. \nIn this thesis we have observed that there likely are differences in the way skeletal muscle myotubes, derived from type 2 diabetic or healthy controls metabolize fatty acids and respond towards various lipids. We have observed that T2D myotubes on average have a reduced capacity for mitochondrial fatty acids oxidation as compared to myotubes derived from healthy donors. During periods of high fatty acid load, this difference in oxidative capacity may either result in ectopic storage of intramyocellular triacylglycerols imTAG or an increased level of fatty acid metabolic intermediates that may further interfere with insulin signaling. Preincubation of myotubes with eicosapentaenoic acid (EPA) resulted in enhanced fatty acid uptake and storage of imTAG, but also reduced levels of total intracellular acyl-CoA with improved glucose oxidation and unchanged insulin mediated glucose uptake. Preincubetion with the sulfur modified fatty acid analogue tetradecylthioacetic acid (TTA) improved mitochondrial fatty acid oxidation in both T2D and control myotubes, and may thus help alleviate this metabolic difference in T2D. TTA given as a supplement to rodents fed a high fat diet for 7 weeks resulted in 40% reduced weight gain and similar marked reductions in white adipose tissue mass. TTA has previously been shown to activate all peroxisomal proliferator activated receptors (PPARs), and the reduced weight gain possibly resulted because of hepatic PPARα activation, increasing energy expenditure through some unknown mechanism likely involving ectopic uncoupling protein 3 (ucp3) expression.
Author: Andreas Wensaas Hvammen
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2251688490