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

Giannaccini G, Betti L, Palego L, Marsili A, Santini F, Pelosini C, Fabbrini L, Schmid L, Giusti L, Maffei M, Lanza M, Cristofaro M, Baroni S, Mauri M, Vitti P, Fierabracci P, Lucacchini A - BMC Neurosci (2013)

Bottom Line: 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.Moreover, this findings may help to elucidate those monoamine-endocrine networks acting on fat storage, adipocyte signaling and energy balance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy, University of Pisa, via Bonanno 6, Pisa 56126-I, Italy. gino.giannaccini@farm.unipi.it.

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.

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SERT parameters and ANOVA analysis. Scattergram plots of a) [3H]-paroxetine Bmax, fmol/mg protein (SERT number) and b) [3H]-paroxetine KD, nM (SERT affinity), obtained in platelets from individuals of the 5 BMI (Kg/m2) groups. Among group ANOVA: p < 0.0001 (all groups); Bonferroni post-hoc tests showed significant tests: (**): OB-IIs vs. NWs; (***): OB-IIIs vs. NWs and (^): OB-III vs. OWs. Each scattergram plot also shows the mean ± SEM.
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Figure 1: SERT parameters and ANOVA analysis. Scattergram plots of a) [3H]-paroxetine Bmax, fmol/mg protein (SERT number) and b) [3H]-paroxetine KD, nM (SERT affinity), obtained in platelets from individuals of the 5 BMI (Kg/m2) groups. Among group ANOVA: p < 0.0001 (all groups); Bonferroni post-hoc tests showed significant tests: (**): OB-IIs vs. NWs; (***): OB-IIIs vs. NWs and (^): OB-III vs. OWs. Each scattergram plot also shows the mean ± SEM.

Mentions: Equilibrium saturation and Scatchard analysis of [3H]-paroxetine specific binding showed a single population of high-affinity recognition sites in platelet membranes from all the subjects under investigation, clearly indicating the labeling of a single protein. The specific binding was about 90% of total binding at the KD concentration. The [3H]-paroxetine Bmax (fmoles/mg protein) values, corresponding to SERT expression in platelet membranes, were: 1311 ± 51.29 (min.-max: 767–1795) in NWs; 1215 ± 59.44 (min.-max: 665–1685) in OWs; 1137 ± 70.36 (min.-max: 700-1700) in OB-Is; 986.4 ± 89.73 (min.-max.: 344–1675) in OB-IIs; 906.8 ± 58.51 (min.-max: 336–1737) in OB-IIIs. The [3H]-paroxetine KD values (nM), corresponding to the SERT protein affinity state for the specific ligand, were: 0.092 ± 0.009 (min.-max: 0.028-0.20) in NWs; 0.073 ± 0.0085 (min.-max: 0.025-0.16) in OWs; 0.076 ± 0.009 (min.-max: 0.03-0.15) in OB-Is; 0.085 ± 0.009 (min.-max: 0.038-0.19) in OB-IIs; 0.077± 0.007 (min.-max: 0.025-0.22) in OB-IIIs. Individual results for [3H]-paroxetine Bmax and KD, obtained from the 5 BMI groups of subjects, are reported in Figure 1(a,b). ANOVA analysis showed a significant difference between the [3H]-paroxetine Bmax means of the 5 BMI groups (p < 0.0001); after the post-hoc Bonferroni correction test, Bmax mean values were significantly reduced in OB subjects class II-III (BMI > 35 kg/m2) vs. NWs (p < 0.01 and p < 0.001, respectively) (Figure 1a); Bmax values were also decreased in OB-IIIs respect to OWs (p < 0.05) (Figure 1a).


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

Giannaccini G, Betti L, Palego L, Marsili A, Santini F, Pelosini C, Fabbrini L, Schmid L, Giusti L, Maffei M, Lanza M, Cristofaro M, Baroni S, Mauri M, Vitti P, Fierabracci P, Lucacchini A - BMC Neurosci (2013)

SERT parameters and ANOVA analysis. Scattergram plots of a) [3H]-paroxetine Bmax, fmol/mg protein (SERT number) and b) [3H]-paroxetine KD, nM (SERT affinity), obtained in platelets from individuals of the 5 BMI (Kg/m2) groups. Among group ANOVA: p < 0.0001 (all groups); Bonferroni post-hoc tests showed significant tests: (**): OB-IIs vs. NWs; (***): OB-IIIs vs. NWs and (^): OB-III vs. OWs. Each scattergram plot also shows the mean ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016247&req=5

Figure 1: SERT parameters and ANOVA analysis. Scattergram plots of a) [3H]-paroxetine Bmax, fmol/mg protein (SERT number) and b) [3H]-paroxetine KD, nM (SERT affinity), obtained in platelets from individuals of the 5 BMI (Kg/m2) groups. Among group ANOVA: p < 0.0001 (all groups); Bonferroni post-hoc tests showed significant tests: (**): OB-IIs vs. NWs; (***): OB-IIIs vs. NWs and (^): OB-III vs. OWs. Each scattergram plot also shows the mean ± SEM.
Mentions: Equilibrium saturation and Scatchard analysis of [3H]-paroxetine specific binding showed a single population of high-affinity recognition sites in platelet membranes from all the subjects under investigation, clearly indicating the labeling of a single protein. The specific binding was about 90% of total binding at the KD concentration. The [3H]-paroxetine Bmax (fmoles/mg protein) values, corresponding to SERT expression in platelet membranes, were: 1311 ± 51.29 (min.-max: 767–1795) in NWs; 1215 ± 59.44 (min.-max: 665–1685) in OWs; 1137 ± 70.36 (min.-max: 700-1700) in OB-Is; 986.4 ± 89.73 (min.-max.: 344–1675) in OB-IIs; 906.8 ± 58.51 (min.-max: 336–1737) in OB-IIIs. The [3H]-paroxetine KD values (nM), corresponding to the SERT protein affinity state for the specific ligand, were: 0.092 ± 0.009 (min.-max: 0.028-0.20) in NWs; 0.073 ± 0.0085 (min.-max: 0.025-0.16) in OWs; 0.076 ± 0.009 (min.-max: 0.03-0.15) in OB-Is; 0.085 ± 0.009 (min.-max: 0.038-0.19) in OB-IIs; 0.077± 0.007 (min.-max: 0.025-0.22) in OB-IIIs. Individual results for [3H]-paroxetine Bmax and KD, obtained from the 5 BMI groups of subjects, are reported in Figure 1(a,b). ANOVA analysis showed a significant difference between the [3H]-paroxetine Bmax means of the 5 BMI groups (p < 0.0001); after the post-hoc Bonferroni correction test, Bmax mean values were significantly reduced in OB subjects class II-III (BMI > 35 kg/m2) vs. NWs (p < 0.01 and p < 0.001, respectively) (Figure 1a); Bmax values were also decreased in OB-IIIs respect to OWs (p < 0.05) (Figure 1a).

Bottom Line: 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.Moreover, this findings may help to elucidate those monoamine-endocrine networks acting on fat storage, adipocyte signaling and energy balance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy, University of Pisa, via Bonanno 6, Pisa 56126-I, Italy. gino.giannaccini@farm.unipi.it.

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.

Show MeSH
Related in: MedlinePlus