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

BMC Neuroscience

Antonio Lucacchini¹  Paola Fierabracci⁵  Paolo Vitti⁴  Mauro Mauri⁴  Stefano Baroni⁴  Mario Cristofaro¹  Mario Lanza¹  Margherita Maffei³  Laura Giusti¹  Lara Schmid¹  Laura Fabbrini²  Caterina Pelosini⁴  Ferruccio Santini⁴  Alessandro Marsili⁴  Lionella Palego⁴  Laura Betti¹  Gino Giannaccini¹ 

[1] Department of Pharmacy, University of Pisa, via Bonanno 6, Pisa 56126-I, Italy;Clinical Pharmacology Unit, University Hospital “Santa Chiara”, Via Savi 10, 56126-I, Pisa, Italy;Insitute of "Fisiologia Clinica", CNR, Via G. Moruzzi 1, 56124, Pisa, Italy;Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126-I, Pisa, Italy;Endocrinology Unit, University Hospital of Cisanello, via Paradisa 2, Pisa, Italy

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

Others  :  1139937
DOI  :  10.1186/1471-2202-14-128

 received in 2013-03-06, accepted in 2013-10-09,  发布年份 2013

【 摘 要 】

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 (B_max)/BMI ratios to overcome both the disparity of women vs. men number and anthropometric differences between sexes.

Results

[³H]-paroxetine B_max (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 B_max and BMI (r = −0.449; P < 0.0001) was demonstrated. Conversely, [³H]-paroxetine K_D (dissociation constant, nM) did not differ among groups. No gender-related variation concerning B_max/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.

【 授权许可】

   
2013 Giannaccini et al.; licensee BioMed Central Ltd.

【 图 表 】

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