The expression of platelet serotonin transporter (SERT) in human obesity
1 Department of Pharmacy, University of Pisa, via Bonanno 6, Pisa 56126-I, Italy
2 Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126-I, Pisa, Italy
3 Clinical Pharmacology Unit, University Hospital “Santa Chiara”, Via Savi 10, 56126-I, Pisa, Italy
4 Insitute of "Fisiologia Clinica", CNR, Via G. Moruzzi 1, 56124, Pisa, Italy
5 Endocrinology Unit, University Hospital of Cisanello, via Paradisa 2, Pisa, Italy
BMC Neuroscience 2013, 14:128 doi:10.1186/1471-2202-14-128Published: 18 October 2013
Serotonin (5-HT) is a well-known modulator of eating behavior. However, the molecular mechanisms linking its action to body weight balance have been only partially elucidated. Since platelets are a suitable peripheral model to study 5-HT transport, metabolism and release, we herein evaluated the expression of the platelet 5-HT re-uptake system (SERT) by [3H]-paroxetine binding assay. A cohort of 114 unrelated individuals (34 males, 80 females; age, mean ± SD: 38.57 ± 12.47 years) without major psychiatric disorders, was recruited following a naturalistic design regarding age or gender and classified accordingly to their body mass index (BMI). Subjects were divided into 5 groups: normal-weight (NW), overweight (OW) and grade I-III obese (OB) individuals. For gender analyses, data were transformed into [3H]-paroxetine density (Bmax)/BMI ratios to overcome both the disparity of women vs. men number and anthropometric differences between sexes.
[3H]-paroxetine Bmax (SERT density, fmol/mg proteins) was reduced in platelet membranes of grade II (p < 0.01) and III (p < 0.001) obese subjects vs. controls and in overweight subjects (p < 0.05) vs. grade III obese individuals. Considering all patients together, a strong negative correlation between Bmax and BMI (r = −0.449; P < 0.0001) was demonstrated. Conversely, [3H]-paroxetine KD (dissociation constant, nM) did not differ among groups. No gender-related variation concerning Bmax/BMI ratios was observed in this cohort of subjects.
The down-regulation of SERT in platelet membranes of severe human obesity (BMI > 35 Kg/m2) confirms the involvement of 5-HT system in body weight gain. Moreover, this findings may help to elucidate those monoamine-endocrine networks acting on fat storage, adipocyte signaling and energy balance. Targeting 5-HT/5-HT-related markers will possibly uncover the existence of human obesity subtypes.