The β3-adrenergic agonist (BRL35135A) acutely increases oxygen consumption and plasma intermediate metabolites in sheep

Abstract

There is evidence that an atypical adrenoreceptor subtype is involved in mediating some of the physiological effects of catecholamines, particularly in some adipose tissue sites. Therefore, three experiments were conducted to determine the metabolic and energetic responses to oral administration of the purported β3-agonist BRL35135A in ruminant lambs. The post-prandial increase in O2 consumption (0.109 versus 0.139 L/min) and CO2 production (0.102 versus 0.127 L/min) at 30 min after feeding was greater (P < 0.05) in the lambs receiving 5 mg of the BRL35135A. Treatment × time interactions over the period between –50 and 220 min indicate significant increases in plasma non-esterified fatty acids (P < 0.001), glucose (P < 0.001) and lactate (P = 0.024) in lambs consuming a single oral dose of 5 mg BRL35135A. In a subsequent experiment there were similar interactions over the period between –120 and 1440 min for non-esterified fatty acids (P < 0.001), glucose (P < 0.001) and lactate (P < 0.001) in lambs consuming a lower oral dose of 1 mg BRL35135A. The effects of BRL35135A on plasma non-esterified fatty acids (P = 0.95), glucose (P = 0.84) and lactate (P = 0.68) were not modified by the β1- and β2-adrenergic antagonist alprenolol suggesting that the effects were mediated via β3-adrenergic receptor subtypes. In conclusion, these experiments indicate that BRL35135A is acutely active in sheep when given with feed, as indicated by increases in respiratory gas exchange and plasma metabolite concentrations.