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

• Published in: British journal of pharmacology 2009-01, Vol.129 (3), p.448-456
• Main Authors: Germack, Renée, Starzec, Anna, Perret, Gérard Y
• Format: Article
• Language: English
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703008

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