MECHANISMS FOR DIFFERENCES IN LIPOLYSIS BETWEEN HUMAN SUBCUTANEOUS AND OMENTAL FAT-CELLS

Catecholamine-regulation of lipolysis and beta-adrenoceptor binding isoterms were studied in human sc and omental isolated fat cells from 24 subjects undergoing elective cholecystectomy. The lipolytic sensitivity of the nonselective beta-agonists epinephrine and isoprenaline as well as the selective agonists norepinephrine (beta-1) and terbutaline (beta-2) was significantly increased 5-10 times in omental fat cells. On the other hand, no regional difference in antilipolytic sensitivity was seen for the alpha-2 agonist clonidine. No regional difference in lipolytic action was seen when measuring the effect of forskolin, (Bu)2cAMP or enprofylline, which act at different postadrenoceptor steps in the lipolytic cascade. Lipolysis data showed no sex differences. A beta-1-pattern was seen in both regions when lipolysis dose-response curves were arranged in order of potency. Radioligand saturation experiments with the nonselective beta-antagonist I-125-cyanopindolol and competition experiments between this radioligand and the selective antagonists CGP-20,712-A (beta-1) and ICI-118551 (beta-2) showed a 2-fold increase in the amount of beta-1- and beta-2-adrenergic receptors in omental as compared to sc fat cells (P < 0.02). Competition studies with the same radioligand and the nonselective beta-agonist isoprenaline showed no regional differences in terms of receptor affinity (K(d) high 10 nM and K(d) low 1-mu-M) or in relative fraction of receptors in the high affinity state (35%). It is concluded that an increased lipolytic sensitivity for beta-1- and beta-2-agonists can be due to an increase in the amount of the two adrenoceptor subtypes in omental fat cells and thereby explain why catecholamines are more lipolytic in omental cells than in sc fat cells.