|
Department of Human Biology, NUTRIM, University of Maastricht
1. Disturbances in fatty acid mobilization and skeletal muscle fatty acid metabolism in obesity and type 2 diabetes mellitus A recent study combining stable isotopes and the forearm muscle balance technique has shown that both the uptake and oxidation of plasma FFA is impaired in type 2 diabetes during postabsorptive condtions and during infusion of the non-selective beta-agonist isoprenaline (ISO). This impairment was accompanied by a lowered content of cytosolic fatty acid binding protein (FABPc, reference 1). Additionally, it was shown that this impairment in the capacity to utilize plasma FFA also extended to a condition of physical exercise (2). These impairments in muscle FFA metabolism may be of importance in the etiology of skeletal muscle insulin resistance in obesity and type 2 DM by promoting intramuscular triglyceride storage. In collaboration with the Huddinge group, we are starting now a project on local muscle and adipose tissue lipolysis during postabsorptive conditions and during catecholamine stimulation in lean and obese subjects, using microdialysis and a stable isotope tracer of glycerol. In collaboration with Oxford, we are starting up a project, investigating muscle fatty acid metabolism and oxidation in the postprandial state during different feeding conditions, using stable isotope tracers. 2. The role of genetic variability in the disturbances in fat metabolism in obesity and type 2 diabetes mellitus In collaboration with the Huddinge group, we are investigating the relation between known polymorphisms of beta2- and beta1-adrenoceptor genes and the in vivo sympathetically mediated fat utilization in obese males. 3. Role of different adrenoceptors in the regulation of lipid mobilization and thermogenesis The in vivo beta3-adrenergic stimulation of human thermogenesis and lipid use was investigated. In this study no evidence could be found for a beta3adrenergically mediated increase in human thermogenesis and lipid use during infusion of the non-selective beta-agonist isoproterenol (3). 4. Effect of weight reduction on disturbed fat metabolism in type 2 diabetes The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 content was studied in type 2 diabetic subjects (4). We found a negative correlation between the change in UCP3 protein content after weight loss and the change in BMI, suggesting that the decrease in UCP3 could prevent further weight loss. Additionally, the change in UCP3 protein content correlated with the change in skeletal muscle FABPc, suggesting a role for UCPs in fat handling. References
|