Inhibition of Fatty Acid Synthesis by Stimulation of α- and β-Adrenergic Receptors in Human Mononuclear Leukocytes

Summary

Selective α- and β-adrenergic agonists and antagonists were used to determine the action of catecholamines on fatty acid biosynthesis in freshly isolated human mononuclear leukocytes. Incubation of cells for 22 h in a lipid-free medium resulted in a 4-fold increase in the incorporation of [¹⁴-C]acetate into fatty acids. Addition of (-)-epinephrine in increasing concentrations to the incubation medium inhibited the rate of fatty acid synthesis by 42 % at a concentration of 0.1M. Similar effects were observed using (-)-norepinephrine and the β-agonist isoproterenol. The catecholamine action was diminished by the unselective β-blocker propranolol and mimicked by dibutyryl cyclic AMP. Since human mononuclear leukocytes possess P2-, but not β1-adrenoceptors (Brodde, Engel and Hoyer 1981), catecholamines may act via β-adrenergic receptors of the β2-subtype. In addition, it appears that stimulation of β-adrenergic receptors inhibits fatty acid synthesis, too. In the presence of a β-blockade by 1 μM propranolol, the α2-agonist α-methylnorepinephrine, but not the α1-agonist phenylephrine inhibited fatty acid synthesis rate. Accordingly, the epinephrine effect was attenuated by the α2-antagonist yohimbine, but not by the α1-antagonist prazosin. The results provide evidence that catecholamines may inhibit the synthesis rate of fatty acids by stimulation of both, β2- and α2-adrenergic receptors.

Key words

Fatty Acid Synthesis - Catecholamines - β2-Adrenergic Receptors - α2-Adrenoceptors - Human Mononuclear Leukocytes