Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women

Abstract

Leptin has been called a hormone of reproduction, and seems to link fat and fertility. It has been speculated that the neurotransmitter norepinephrine (NE) (noradrenaline), possibly via the sympathetic nervous system, may represent the afferent signal which modulates leptin release from adipocytes. The purpose of this study was to produce a state of decreased sympathetic output by using the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this compound on the secretion of leptin from fat cells. Ten subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks using a randomized, double-blind, placebo-controlled, cross-over design. Blood samples for hormone measurements were obtained over 24 h (18 time points) on day 2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P < 0.05). Plasma leptin concentrations measured in the control group in women and men were similar to those reported previously in lean subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes with an increase of nocturnal concentrations by approximately 50%. Two-way analysis of variance reveals no significant difference in leptin secretion between the control and active groups in women and men. In summary, preliminary results do not support the hypothesis that NE represents the afferent signal from the central nervous system which modulates leptin release from adipocytes in the human. Further studies are needed to define the role of the sympathetic nervous system as well as NE in the regulation of leptin secretion and its involvement in obesity and reproduction.

Serum Leptin During Recovery Following Maximal Incremental and Prolonged Exercise

“…In resting rodents catecholamines and other β-adrenergic agonists inhibit leptin production and mRNA expression [11,20,29], however, human data are limited and still controversial. Zimmerman et al reported that prolonged inhibition of catecholamine synthesis in normal-weight men and women, did not affect serum leptin levels [46], while in the Pinkney et al study 90 -120 minutes of isoprenaline reduced plasma leptin [33]. In two other investigations plasma catecholamine levels were not related to serum leptin levels in men [24,28] but were significantly correlated to leptin in cycling women [28].…”

Monoamine depletion in psychiatric and healthy populations: review

“…84,106 Leptin secretion was not affected by AMPT. 107 No studies were found that investigated the effects on neuroendocrine measures in patient samples.…”

Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors

“…There is now the ®rst evidence from in vitro and clinical studies for a suppressive effect of catecholamines on leptin secretion in humans (17±23), although some discrepancies remain not fully resolved (24,25). However, to date, it is still unde®ned which speci®c adrenoceptor subtypes are responsible for the inhibition of leptin release from human adipocytes.…”