Studies on the regulation of human skeletal muscle lipolysis in vivo

Abstract: Intramuscular triglyceride deposits are a significant energy source, and are considered to be of importance in the pathogenesis of skeletal muscle insulin resistance. In contrast to adipose tissue, the lipolytic process in skeletal muscle is not well characterised. Lipolysis in adipose tissue is stimulated by catecholamines, suppressed by insulin and is known to vary between different regions. The aim of this thesis was to study skeletal muscle lipolysis by determining whether the lipolytic activity differs among various muscle groups and by investigating the hormonal regulation of skeletal muscle lipolysis with reference to catecholamines and insulin. Adipose tissue was studied for comparison. The microdialysis technique was used for sampling of interstitial glycerol (index of lipolysis), and measurement of the fractional glycerol release. The local nutritive blood flow was assessed by either the 133 Xe-clearance or the ethanol perfusion techniques. There were marked variations in lipolytic activity among different muscle groups in healthy, non-obese humans at rest. Net glycerol release was registered in the gastrocnemius muscle but not the deltoid and quadriceps femoris (vastus lateralis) muscles. Analysis of muscle biopsies showed that the differences in lipolysis rates are probably related to muscle fibre composition; a significant lipolytic activity being demonstrable in the muscle with type I fibre dominance. The effect of insulin and the possible influence of the prevailing glucose levels on muscle lipolysis were studied in a group of male diabetic patients. No antilipolytic effect was seen in skeletal muscle during normal glycemic conditions. However, hyperinsulinemia in combination with moderate hyperglycemia reduced the lipolytic activity in skeletal muscle in a similar way as in adipose tissue. This indicates a glucose-mediated potentiation of the antilipolytic effect of insulin in both skeletal muscle and adipose tissue. Hypoglycemia-induced catecholamine release resulted in a transient (tachyphylaxia) stimulation of skeletal muscle lipolysis whereas no effects on the lipolytic activity were seen in response to iv noradrenaline infusion in healthy, non-obese subjects. In adipose tissue the lipolysis rates increased in both situations, as expected. In situ perfusion of the hormones showed considerably more pronounced lipolytic response and higher sensitivity to adrenaline than to noradrenaline in skeletal muscle. In adipose tissue, in situ perfusion indicated higher sensitivity to noradrenaline. In conclusion, skeletal muscle lipolysis varies between different muscle groups, probably due to fiber composition. The hormonal regulation of lipolysis in skeletal muscle differs markedly from that in adipose tissue. In skeletal muscle, insulin posses no appreciable antilipolytic effect and adrenaline rather than noradrenaline appears to be the main stimulator of lipolysis.