Abstract

Catecholamines are major stimulants of adipose tissue metabolism. Norepinephrine and epinephrine act through three subtypes of β-adrenoceptors (β-AR) expressed in the adipocytes. The aim of this work was to study the mechanisms of lipid mobilization in β₁/β₂/β₃-AR triple-knockout (β-less) mice. Glycerol and nonesterified fatty acids released from isolated adipocytes were measured as an index of lipolytic activity. There was no difference between the two genotypes for basal lipolysis and lipolytic response to corticotropin or to agents acting at the adenylyl cyclase and protein kinase A levels. The lipolytic response to norepinephrine and β-AR agonists was blunted in β-less mice. However, a residual low-affinity lipolytic effect was observed in the presence of catecholamines and β₃-AR agonists but not of β₁- or β₂-AR agonists. cAMP levels were increased by a β-AR agonist in white and brown adipocytes of β-less mice. The residual lipolytic effect was blocked by β-AR antagonists. It was mediated neither by α₁- or α₂-AR nor dopaminergic, serotonergic, and histaminergic by receptors. Bioinformatic analyses do not provide evidence for a fourth β-AR. We conclude that the residual lipolytic effect observed in β-less mice can be attributed to an unknown Gs-protein-coupled receptor with low affinity for catecholamines.