Regulation of β 1 ‐ and β 3 ‐adrenergic agonist‐stimulated lipolytic response in hyperthyroid and hypothyroid rat white adipocytes

This study examined the effects of thyroid status on the lipolytic responses of rat white adipocytes to β‐adrenoceptor (β‐AR) stimulation. The β 1 ‐ and β 3 ‐AR mRNAs and proteins were measured by Northern and saturation analyses, respectively. Glycerol production and adenyl cyclase (AC) activity induced by various non‐selective and selective β 1 /β 3 ‐AR agonists and drugs which act distal to the receptor in the signalling cascade were measured in cells from untreated, tri‐iodothyronine (T 3 )‐treated and thyroidectomized rats. The β 3 ‐AR density was enhanced (72%) by T 3 ‐treatment and reduced (50%) by introduction of a hypothyroid state while β 1 ‐AR number remained unaffected. The β 1 ‐ and β 3 ‐AR density was correlated with the specific mRNA level in all thyroid status. The lipolytic responses to isoprenaline, noradrenaline (β 1 /β 3 /β 3 ‐AR agonists) and BRL 37344 (β 3 ‐AR agonist) were potentiated by 48, 58 and 48%, respectively in hyperthyroidism and reduced by about 80% in hypothyroidism. T 3 ‐treatment increased the maximal lipolytic response to the partial β 3 ‐AR (CGP 12177) and β 1 ‐AR (xamoterol) agonists by 234 and 260%, respectively, increasing their efficacy (intrinsic activity: 0.95 versus 0.43 and 1.02 versus 0.42). The maximal AC response to these agonists was increased by 84 and 58%, respectively, without changing their efficacy. In the hypothyroid state, the maximal lipolytic and AC responses were decreased with CGP (0.17±0.03 versus 0.41±0.08 μmol glycerol/10 6 adipocytes; 0.048±0.005 versus 0.114±0.006 pmol cyclic AMP min −1  mg −1 ) but not changed with xamoterol. The changes in lipolytic responses to postreceptor‐acting agents (forskolin, enprofylline and dibutenyl cyclic AMP, (Bu) 2 cAMP) suggest the modifications on receptor coupling and phosphodiesterase levels in both thyroid states. Thyroid status affects lipolysis by modifying β 3 ‐AR density and postreceptor events without changes in the β 1 ‐AR functionality.British Journal of Pharmacology (2000) 129 , 448–456; doi: 10.1038/sj.bjp.0703008