Thermogenic responses to adrenoceptor agonists and brown fat adrenoceptors in overfed rats

Rats fed a cafeteria diet to produce hyperphagia showed increases in the maximal thermogenic responses (rise in oxygen consumption) to isoprenaline (mixed beta-agonist), prenalterol (beta 1-selective agonist) and clenbuterol (beta 2-agonist), and left-shifts in the dose-response curves to the latter two. The maximal response to phenylephrine (alpha-agonist) was similar for control and cafeteria rats. Ligand binding studies revealed increases in beta-adrenoceptor density of 33-38% in brown fat cells and isolated membranes from cafeteria-fed rats, but a 30% reduction in beta-receptors in heart membranes. Cold-adaptation caused a 22% reduction in beta-receptor density in brown fat membranes, but no change in heart. The ratio of beta 1/beta 2-receptors in brown fat was reduced from 59/45 in control to 47/54 in cafeteria-fed rats, but was not significantly altered in heart (58/44) or in brown fat from cold-adapted animals (64/30). alpha-Adrenoceptor density was increased above control values by 69 and 25% in brown adipose tissue from cafeteria and cold-adapted rats, respectively.