Effect of gender on

platelet serotonin
transporter
expression in class
III obese
individuals
Serotonin (5-HT) is a modulator of eating behavior.
This endogenous amine is tightly involved in the
regulation of feeding behavior at hypothalamic level
acting within the ventromedial and lateral nuclei [1-
3]. On the other side, glucocorticoid response
influences monoamine/5-HT transmission and
receptor function in the central nervous system
(CNS), thus affecting feeding behavior and
macronutrient choise [4-7]. In particular, 5-HT
transporter (SERT) is a pivotal membrane-bond
glycoprotein acting during 5-HT transmission (Fig.
1).







However, the role of 5-HT system in the control of
human body weight is still under investigations.
A significant negative correlation between the
density of SERT ([
3
H]paroxetine, B
max
fomol/mg
protein)and body mass index (BMI) has been
observed in platelet of five groups with divergent
body weight [8,9].
The present study is an deepening of our previous
[
3
H]paroxetine binding investigation: were now
evaluated the effect of gender on platelet SERT
expression in class III obese invididuals.
Methods
Subjects
The study was carried out in a cohort of 32 grade
III obese (OB) individuals (table 1) without major
psychiatric disorders, recruited and classified
according to their body mass index (BMI) .
L. Betti
1
, L. Palego
2
, A. Marsili
2
, F. Santini
2
,
A. Lucacchini
1
, G. Giannaccini
1

Background
Results
Conclusion
References
Funding Source:
The present work has
been supported by
Ministero dellIstruzione
dellUniversit e della
Ricerca (MIUR)-As grants
to Prof. Giannaccini
The down-regulation of SERT in platelet
membranes of severe human obese
individuals (BMI 40 Kg/m
2
) confirms the
involvement of 5-HT system in body weight
gain [9]. Present results show that neither
SERT density not affinity appreciably differ
between sexes. Nevertheless, the divergent
correlation between SERT density and BMI in
women vs. men suggests that this aspect
should deserve attention and, possibly, more
investigations.
Accordingly to preliminary data [9],
[
3
H]paroxetine B
max
was found reduced in
platelet membranes of both comparison groups
vs. respective controls; conversely,
[
3
H]paroxetine K
d
did not differ (data not
shown). Table 2 instead presents data showing
the direct comparison of SERT binding
parameters of OB class III men vs. women.
Despite a trend towards higher mean B
max

value in men, no significant gender difference
was reported for any parameters.
Figure 1. Serotonin transporter.
1
Department of Pharmacy;
2
Department of Clinical and
Experimental Medicine. University of Pisa. Pisa, Italy
4
3
1
2
5
1. Leibowitz SF, Alexander JT, (1989) Biol.
Psychiatry 44: 851-864 .
2. Schwartz DH, Hernandez L, Hoebel BG (1990)
Brain Res Bull. 25: 797-802.
3. Blundell JE (1992) Am J. Clin. Nutr. 55: 1555-
1595.
4. Ely DR, Sapper V, Marasca J, Correa JB, Gamaro
GD, Xavier MH (1997) Physiol. Behav. 61: 395-
398.
5. Van der Kar LD, Blair ML, (1999) Front.
Neuroendocrinol. 20: 1-48..
6. Carrasco GA, Vab der Kar LD (2003) Eur. J
Pharmacol. 463: 235-272.
7. Torres S, Nowson C (2007) Nutr. 23: 887-894.
8. Betti L, Italiani P, Fabbrini L, Baroni S, Mascia G,
Pelosini C, Biddau M, Santini F, Lucacchini A,
Giannaccini G (2004) It J Biochem. 53: 281.
9. Giannaccini G, Betti L, Palego L, et al., (2013)
BMC Neuroscience 14: 1-8.
neurvous impulse
autoreceptor
autoreceptor
release
of serotonin
degradation
by MAO
vescicles
ionic channel
Gi/s
receptor
reuptake
GTP GDP
GTP
GDP
receptor
Gq
AC
PLC
serotonin transporter
Cl- 5-HT+ Na+ K+
K
+
K+
K
+
[3H]paroxetine binding experiments
Whole venous blood samples (25 ml) were
drawn from overnight fasting subjects between
8:00 and 9:00 am into plastic tubes containing
anticoagulant (sodium citrate 2.2%, citric acid
1.2%).
Samples were then processed for:
platelet preparation;
membrane preparation;
binding studies (to determine SERT binding
parameters: maximal binding capacity, B
max
,
fmol/mg protein; dissociation constant, K
d
, nM),
as described by Giannaccini et al., 2013 [9].
Table 1. Subjects recruited for the study. Data are presented as
mean SEM and ranges (minimum and maximum values).
Age (y) 42.2 3.8 42.5 2.4
(26-59) (22-59)
BMI (Kg/m
2
) 46.2 1.3 46.2 0.7
(40-54.3) (41-54.8)
Men, n = 10 Women, n = 22
Table 2. Gender effect on subjects bindig parameters. Data
are presented as mean SEM and ranges (minimum and
maximum values).
B
max
(fmol/mg) 1054 95.5 937 70.8
(606-1541) (347-1737)
K
d
(nM) 0.06 0.006 0.08 0.009
(0.028-0.09) (0.025-0.22)
Men, n = 10 Women, n = 22
Besides, to overcome the disparity of woman
vs. men number as well as anthropometric
differences between sexes, data were further
transformed into (B
max
)/BMI ratios (Fig. 2). No
gender related variation concerning B
max
/BMI
ratios was observed in our subjects.
Figure 3. Correlation of platelet SERT density with BMI
by gender. A) Men (n = 10). B) (n = 22): panel inside
figure report the Pearson r coefficient and its statistical
significance. Line represents data linear fit from linear
regression analysis
A)
B)
Pearson r -0.5029
P value ***
Class
III OB
Willendorf
BMI > 40 Kg/m
2
Bagnante che si asciuga una gamba
di Pierre Auguste Renoire
Alessandro dal Borro
di Andrea Sacchi
Despite such results, present sub-analysis
revealed a significant negative correlation
between [
3
H]paroxetine B
max
and BMI in
women only (r= -0.5029; p> 0.001, Fig. 3B).
For this comparison, normal-weight subjects
were also included .
Obese subjects were recruited among the patients
of the Obesity Center, University of Pisa and all
signed a regular informed consent approved by
the Ethics Committee of the Pisa University.
Figure 2. Comparison of [
3
H]paroxetine B
max
/BMI ratios in
males and females. Each scattergram plot shows the
mean SEM.