Hyperleptinaemia in mice induced by administration of the tyrosine hydroxylase inhibitor α-methyl-p-tyrosine

alpha-methyl-p-tyrosine (alpha MPT), an inhibitor of tyrosine hydroxylase, was administered to mice to block noradrenaline synthesis. Ten hours 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 also increased, but UCP1 mRNA in brown fat fell. In contrast to lean mice, 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. Hyperleptinaemia was attenuated by treatment with a beta(3)-adrenoceptor agonist, Inhibition of noradrenaline synthesis leads to the rapid induction of hyperleptinaemia; it is suggested that sympathetic tone plays a pivotal role in regulating leptin production. (C) 1998 Federation of European Biochemical Societies.