Influence of the beta 2-adrenergic agonist clenbuterol on insulin-stimulated lipogenesis in mouse adipocytes

Growing mice fed the beta 2-adrenergic agonist clenbuterol (CB; 20ppm) had increased rate of growth and altered composition of gain (greater protein and less fat). Adipocytes prepared from the epididymal fat pads of treated and untreated mice were used to examine the influence of CB on lipid metabolism. Using cells from untreated mice, CB stimulated lipolysis to an equivalent maximum rate as epinephrine (EPI), but CB was far less potent (EC50 (microM); CB = 5, EPI = 0.2). Both CB and EPI inhibited insulin-stimulated lipogenesis over the physiological range of insulin concentrations. This inhibition was expressed as a dose-dependent decrease in tissue sensitivity to insulin and a decrease in maximal lipogenic capacity. Inhibition of maximal rate, but not of insulin sensitivity, could be stimulated by the addition of palmitate without EPI or CB. Adipocytes isolated from CB-treated mice did not differ from controls in sensitivity to insulin or in activity of fatty acid synthetase. Increased lipolysis and reduced lipogenesis as observed in vitro with CB are consistent with reduced fat accretion in CB-treated mice. However, the absence of detectable changes in adipocyte lipogenesis from CB-fed mice leaves open the question of the relevance of altered lipid metabolism to the observed changes in body composition.