Studies of adipose tissue in humans with special reference to innervation by the sympathetic nervous system

Abstract

This thesis reports the effects in vivo of the sympathetic nervous system (SNS) in human subcutaneous abdominal white adipose tissue (WAT) and other tissues involved in energy storage and utilisation. Cannulation of superficial veins draining skin, abdominal subcutaneous WAT and deep forearm muscle combined with isotope turnover methodology and tissue blood flow estimation was used to investigate the behaviour of these tissues under varying experimental conditions. Glucose infusion study: This examined differential substrate uptake and utilisation in the three tissues. WAT was responsible for only a small amount of glucose disposal and deep forearm muscle took up but did not release NEFA. Skin was a net exporter of lactate. Results confirm the relative purity of the venous effluent from these tissues. Sympathetic Nervous System study: This examined whole body, WAT and forearm muscle SNS activity in lean and obese individuals under fasting and postprandial conditions. Whereas whole body SNS activity was increased in the obese, regional heterogeneity of SNS activity was evidenced by reduced SNS activity in WAT. Adipose tissue blood flow was significantly reduced in the obese. This may underlie abnormal lipolysis and/or blood flow regulation in obesity. 7 Pulsatility Studies: These studies examined whether lipolysis and leptin production in human WAT is uniform or pulsatile. Novel control datasets were used to test the robustness of a widely used pulse detection algorithm. Whereas NEFA release appeared truly pulsatile, apparent leptin ‘pulses’ occurred with similar frequency in the control datasets and appear likely simply to reflect variability. Anatomical studies: Confocal immuno-fluorescence microscopy was used to demonstrate innervation of WAT in man for the first time. Such innervation appears confined to the microvasculature and suggests that the defective SNS activity within WAT is likely to affect adipose tissue biology primarily through defective regulation of adipose tissue blood flow.