title: The expression of platelet serotonin transporter (SERT) in human obesity.
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.
authors.affiliation: Department of Pharmacy, University of Pisa, via Bonanno 6, Pisa 56126-I, Italy. gino.giannaccini@farm.unipi.it.
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Lionella
authors.initials: L
authors.lastname: Palego
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marsili
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Santini
authors.forename: Caterina
authors.initials: C
authors.lastname: Pelosini
authors.forename: Laura
authors.initials: L
authors.lastname: Fabbrini
authors.forename: Lara
authors.initials: L
authors.lastname: Schmid
authors.forename: Laura
authors.initials: L
authors.lastname: Giusti
authors.forename: Margherita
authors.initials: M
authors.lastname: Maffei
authors.forename: Mario
authors.initials: M
authors.lastname: Lanza
authors.forename: Mario
authors.initials: M
authors.lastname: Cristofaro
authors.forename: Stefano
authors.initials: S
authors.lastname: Baroni
authors.forename: Mauro
authors.initials: M
authors.lastname: Mauri
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Paola
authors.initials: P
authors.lastname: Fierabracci
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins