THE SYMPATHETIC NERVOUS-SYSTEM AS A TARGET FOR INTERVENTION IN OBESITY

The sympathoadrenal system plays an important role in the regulation o f both energy intake and energy expenditure (EE), and the sympathetic nervous system (SNS) offers a dual target for pharmacological interven tion directed at weight loss in obese patients. The sizes of the fat-f ree mass and fat mass are the major determinants of resting EE, but st udies using different techniques have shown that differences in sympat hetic activity can account for an additional proportion of the variati on between individuals. Differences in thermogenic responses to food c an also be explained by different abilities to activate the sympathoad renal system. A low resting EE for a given body composition is one man ifestation of the genetically determined predisposition to obesity, A low sympathetic activity may be one factor responsible but, as yet, no conclusive evidence has been found, In dietary treatment programmes o f obesity, patients with high levels of EE and greater SNS activity ac hieve greater long-term weight loss than those with lower levels. Phar macological stimulation with sympathomimetic compounds suppresses appe tite and increases energy expenditure through stimulation of beta(1), beta(2) and beta(3)-receptor subtypes, During chronic treatment, the b eta(3)-mediation may predominate due to down-regulation of beta(1)- an d beta(2)-receptors. An improved understanding of the aetiological rol e of the SNS in the development of obesity in genetically susceptible individuals may permit tailoring of pharmacological intervention.