Role of β1- and β3-adrenoceptors in the regulation of lipolysis and thermogenesis in rat brown adipocytes

Abstract

To evaluate the physiological functions of β1-, β2-, and β3-adrenoceptors (ARs) in brown adipose tissue, the lipolytic and respiratory effects of various adrenergic agonists and antagonists were studied in rat brown adipocytes. The β-agonists stimulated both lipolysis and respiration (8–10 times above basal levels), with the following order of potency (concentration eliciting 50% of maximum response): CL-316243 (β3) > BRL-37344 (β3) > isoproterenol (mainly β1/β2) > norepinephrine (NE; mainly β1/β2) > epinephrine (mainly β1/β2) ≫ dobutamine (β1) ≫ procaterol (β2). Schild plot coefficients of competitive inhibition experiments using ICI-89406 (β1 antagonist) revealed that more than one type of receptor mediates NE action. It is concluded from our results that 1) NE, at low plasma levels (1–25 nM), stimulates lipolysis and respiration mainly through β1-ARs, 2) NE, at higher levels, stimulates lipolysis and respiration via both β1- and β3-ARs, 3) β2-ARs play only a minor role, and 4) β3-ARs may represent the physiological receptors for the high NE concentrations in the synaptic cleft, where the high-affinity β1-ARs are presumably desensitized. It is also suggested that lipolysis represents the flux-generating step regulating mitochondrial respiration.