Open Access Highly Accessed Research article

The expression of platelet serotonin transporter (SERT) in human obesity

Gino Giannaccini1*, Laura Betti1, Lionella Palego2, Alessandro Marsili2, Ferruccio Santini2, Caterina Pelosini2, Laura Fabbrini3, Lara Schmid1, Laura Giusti1, Margherita Maffei4, Mario Lanza1, Mario Cristofaro1, Stefano Baroni2, Mauro Mauri2, Paolo Vitti2, Paola Fierabracci5 and Antonio Lucacchini1

Author Affiliations

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

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BMC Neuroscience 2013, 14:128  doi:10.1186/1471-2202-14-128

Published: 18 October 2013

Abstract

Background

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.

Results

[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.

Conclusions

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.

Keywords:
Human obesity; SERT expression; [3H]-paroxetine binding; Platelets