Importance of beta-adrenoceptor function in fat cells for lipid mobilization.

The role of peripheral catecholamine sensitivity in lipid mobilization was investigated in 78 healthy non-obese subjects by comparing beta-adrenergic regulation of lipolysis in isolated adipocytes with circulating catecholamines and glycerol (lipolysis index). Small intra-individual variations (5-7%) in adipocyte lipolytic beta-adrenoceptor sensitivity (ED50) for isoprenaline were found. However, large inter-individual variations (almost 10(5)-fold) in isoprenaline ED50 were observed in abdominal or gluteal adipocytes, which correlated (r = 0.52) negatively with the resting plasma noradrenaline levels. A correlation was also observed between circulating noradrenaline and adipocyte ED50 for noradrenaline (r = -0.38). In subjects with high (ED50 less than 10(-11) mol l-1) as compared to low isoprenaline sensitivity (ED50 greater than 10(-10) mol l-1) physical exercise induced a two times greater increase in plasma glycerol (P less than 0.01), in spite of a 50% less marked increase of plasma noradrenaline (P less than 0.01). Findings with beta-adrenoceptor mRNA and with total beta-adrenoceptor number or affinity for agonist did not show any strong correlation with the resting plasma noradrenaline level (r less than 0.25). In conclusion, inter-individual variations in beta-adrenoceptor sensitivity and its relation to circulating noradrenaline can be ascribed to specific modulations of either BAR-subtypes or in the postreceptor activation of lipolysis. These variations in adipocyte beta-adrenoceptor sensitivity may participate in the regulation of peripheral nervous activity and play a putative role in lipolysis during exercise when subjects with high beta-adrenoceptor sensitivity increased their ability to mobilize lipids despite a reduced noradrenaline response.