Human obesity is associated with a chronic elevation in brain 5-hydroxytryptamine turnover

The afferent signals that evoke changes in energy intake with regard to bod y weight regulation are presumed to arise partly from body stores, with the most likely candidate being adipose tissue depots. However, clinical inves tigation of the neuronal circuitry involved in the central nervous system's processing of such satiety signals remains largely unexplored. Using percu taneously placed catheters in either the right or left internal jugular vei ns, we were able to quantify the release of central nervous system monoamin e and indoleamine neurotransmitters in 64 weight-stable male subjects with varying degrees of adiposity. Veno-arterial plasma concentration difference s and internal jugular blood or plasma flow were used, according to the Fic k Principle, to quantify the amount of neurotransmitter stemming from the b rain. By combining this technique with a noradrenaline and adrenaline isoto pe dilution method for examining neuronal transmitter release, we were able to examine the association between central nervous system neurotransmitter s and efferent sympathetic nervous outflow and adrenomedullary function in human obesity. We found that brain 5-hydroxytryptamine (serotonin) turnover is chronically elevated in proportion to adiposity and is increased postpr andially to a similar degree in lean and obese individuals. There was no di fference in the deg ree of sym pathetic nervous activity or rate of adrenal ine secretion in the subjects examined. It therefore seems that in human ob esity, in the face of a chronic elevation in peripheral satiety signals, br ain serotonergic processes are switched on accordingly, but the subsequent physiological response involving a reduction in food intake, increased ther mogenesis and sympathetic activity is in some way impeded.