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

Alpha-methyl-p-tyrosine (alphaMPT), an inhibitor of tyrosine hydroxylase, was administered to mice to block noradrenaline synthesis. Ten hours after injection of alphaMPT there was a 6-fold increase in plasma leptin. The level of ob mRNA in epididymal white adipose tissue was also increased, but UCP1 mRNA in brown fat fell. In contrast to lean mice, ob mRNA in white fat of ob/ob mice was not increased by alphaMPT. AlphaMPT raised plasma leptin in fasted as well as fed mice. Hyperleptinaemia was attenuated by treatment with a beta3-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.