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

Abstractα-methyl-p-tyrosine (αMPT), an inhibitor of tyrosine hydroxylase, was administered to mice to block noradrenaline synthesis. Ten hours after injection of αMPT 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 αMPT. αMPT raised plasma leptin in fasted as well as fed mice. Hyperleptinaemia was attenuated by treatment with a β3-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

Regulation of leptin receptor and NPY gene expression in hypothalamus of leptin-treated obese (ob/ob) and cold-exposed lean mice

AbstractLeptin receptor gene expression has been measured in arcuate and ventromedial hypothalamic nuclei. Receptor mRNA in both hypothalamic areas was higher in obese mice than in lean littermates. Twice daily leptin administration for 7 days profoundly affected food intake, reduced leptin receptor mRNA in the arcuate nucleus, and had a similar effect on neuropeptide Y gene expression. A single leptin injection was ineffective. Exposure of lean mice to cold for 24 h caused an induction of leptin receptor and NPY mRNA which was normalized when animals were returned to the warm. Regulation of receptor gene expression may be an important component in the reading of the leptin signal