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

作者：Giannaccini Gino^*; Betti Laura; Palego Lionella; Marsili Alessandro; Santini Ferruccio; Pelosini Caterina; Fabbrini Laura; Schmid Lara; Giusti Laura; Maffei Margherita; Lanza Mario; Cristofaro Mario; Baroni Stefano; Mauri Mauro; Vitti Paolo; Fierabracci Paola; Lucacchini Antonio

来源：BMC Neuroscience, 2013, 14(1): 128.

DOI：10.1186/1471-2202-14-128

• Human obesity
• SERT expression
• [H-3]-paroxetine binding
• Platelets

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 [H-3]-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 [H-3]-paroxetine density (B-max)/BMI ratios to overcome both the disparity of women vs. men number and anthropometric differences between sexes. %26lt;br%26gt;Results: [H-3]-paroxetine B-max (SERT density, fmol/mg proteins) was reduced in platelet membranes of grade II (p %26lt; 0.01) and III (p %26lt; 0.001) obese subjects vs. controls and in overweight subjects (p %26lt; 0.05) vs. grade III obese individuals. Considering all patients together, a strong negative correlation between B-max and BMI (r = -0.449; P %26lt; 0.0001) was demonstrated. Conversely, [H-3]-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. %26lt;br%26gt;Conclusions: The down-regulation of SERT in platelet membranes of severe human obesity (BMI %26gt; 35 Kg/m(2)) 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.

• 出版日期2013-10-18