Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition

The effects of adrenaline, noradrenaline, and of the alpha 2- and beta-selective agonists clonidine and isoproterenol were studied in fifteen obese subjects before and after 4 weeks of caloric restriction (300 cal day-1). Basal glycerol release averaged 1.4 mumol (10(6) cells)-1 (180 min)-1 before starvation and 2.8 mumol (10(6) cells)-1 (180 min)-1 during starvation (P less than or equal to 0.1). Before starvation adrenaline and noradrenaline caused a 2-3-fold increase of glycerol release. This lipolytic effect disappeared during starvation. An inhibitory effect of adrenaline was observed instead which was maximal at an adrenaline concentration of 1 mumol 1(-1) (P less than or equal to 0.05). The dose-response relationships of the alpha 2- and beta-selective agents clonidine and isoproterenol were not appreciably changed by caloric restriction. The increase of basal lipolytic rate and the reversal of adrenaline action seen during caloric restriction could be mimicked by removal of endogenous adenosine using adenosine deaminase (1.6 microgram ml-1). In addition, inclusion of N6-phenylisopropyladenosine (1 mumol 1(-1)) into the medium reverted the adrenaline-induced inhibition seen during caloric restriction. The results suggest that local modulators such as adenosine are of primary importance for the apparent change of responsiveness to adrenaline and noradrenaline seen during starvation of human fat cells in vitro.