Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women |
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Authors: | Zimmermann RC; Krahn L; Rahmanie N; Sauer MV |
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Institution: | Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA. |
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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.
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