Effect of clonidine on the thermic effect of feeding in humans

Previous studies in humans attempting to assess the role of the sympathetic nervous system (SNS) in the thermic effect of feeding (TEF) have investigated the effect of oral or intravenous propranolol on TEF. This approach is potentially limited, however, because of the direct effects of propranolol on catecholamine and thyroid metabolism. In the present study we chose instead to evaluate the effect of clonidine, a centrally acting alpha 2-adrenergic receptor agonist that inhibits SNS outflow, on TEF and SNS activity as reflected by both plasma catecholamines and norepinephrine (NE) kinetics. The TEF and SNS response to an 800-kcal high-carbohydrate liquid meal (85% carbohydrate, 15% protein) was studied in eight healthy male subjects (27 +/- 6 yr) on two separate occasions with the subjects wearing either a clonidine or placebo skin patch for 48 h prior to study. Clonidine significantly suppressed base-line plasma NE concentration (-46%, P less than 0.01) and NE appearance rate (-47%, P = 0.01) compared with placebo, whereas there was no significant effect on epinephrine concentrations, NE clearance rate, or base-line energy expenditure. The expected increments in plasma NE and NE appearance after a meal were also reduced by 54% (P less than 0.05) and 70% (P less than 0.01) of placebo values, respectively, after clonidine. Associated with this reduced SNS response to the meal was a blunting of the expected TEF by 33% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)