HYPERLEPTINAEMIA IN MICE INDUCED BY ADMINISTRATION OF THE TYROSINE-HYDROXYLASE INHIBITOR ALPHA-METHYL-P-TYROSINE

alpha-methyl-p-tyrosine (alpha MPT), an inhibitor of tyrosine hydroxyl ase, was administered to mice to block noradrenaline synthesis. Ten ho urs after injection of alpha MPT there was a 6-fold increase in plasma leptin. The level of ob mRNA in epididymal white adipose tissue mas a lso increased, but UCP1 mRNA in brown fat fell. In contrast to lean mi ce, ob mRNA in white fat of oblob mice was not increased by alpha MPT. alpha MPT raised plasma leptin in fasted as well as fed mice. Hyperle ptinaemia was attenuated by treatment with a beta(3)-adrenoceptor agon ist, Inhibition of noradrenaline synthesis leads to the rapid inductio n of hyperleptinaemia; it is suggested that sympathetic tone plays a p ivotal role in regulating leptin production. (C) 1998 Federation of Eu ropean Biochemical Societies.