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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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Correlations of platelet SERT density with BMI (Kg/m2) by gender. Correlation analysis between [3H]-paroxetine Bmax (fmol/mg protein) with BMI in a) women (n=80) and b) men (n=34). Panels inside figures report the Pearson r coefficient and its statistical significance. Lines in a) and b) represents data linear fit from linear regression analysis.
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Figure 3: Correlations of platelet SERT density with BMI (Kg/m2) by gender. Correlation analysis between [3H]-paroxetine Bmax (fmol/mg protein) with BMI in a) women (n=80) and b) men (n=34). Panels inside figures report the Pearson r coefficient and its statistical significance. Lines in a) and b) represents data linear fit from linear regression analysis.

Mentions: Among-groups differences in SERT expression were additionally sustained by the significant negative correlation between [3H]-paroxetine Bmax and BMI both in the whole cohort (r: -0.449, p < 0.0001; Figure 2a) and by gender sub-analysis in women (r = −0.4178 ; p = 0.0001; Figure 3a) and men ( r = −0.52 ; p = 0.0017; Figure 3b). No significant gender related differences in subjects’ variables (Table 2), as well as in Bmax/BMI ratio (fmol m2 /mg Kg) were found (p = ns), (Figure 4). The Bmax/BMI ratio was: 39.12 ± 3.11 (min.-max: 9.33-74.80) in men and 36.53 ± 2.21 (min.-max:7.92-87.06) in women. No significant variation was reported in SERT affinity (KD) among the BMI based groups (Figures 1b and 2b).


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)

Correlations of platelet SERT density with BMI (Kg/m2) by gender. Correlation analysis between [3H]-paroxetine Bmax (fmol/mg protein) with BMI in a) women (n=80) and b) men (n=34). Panels inside figures report the Pearson r coefficient and its statistical significance. Lines in a) and b) represents data linear fit from linear regression analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Correlations of platelet SERT density with BMI (Kg/m2) by gender. Correlation analysis between [3H]-paroxetine Bmax (fmol/mg protein) with BMI in a) women (n=80) and b) men (n=34). Panels inside figures report the Pearson r coefficient and its statistical significance. Lines in a) and b) represents data linear fit from linear regression analysis.
Mentions: Among-groups differences in SERT expression were additionally sustained by the significant negative correlation between [3H]-paroxetine Bmax and BMI both in the whole cohort (r: -0.449, p < 0.0001; Figure 2a) and by gender sub-analysis in women (r = −0.4178 ; p = 0.0001; Figure 3a) and men ( r = −0.52 ; p = 0.0017; Figure 3b). No significant gender related differences in subjects’ variables (Table 2), as well as in Bmax/BMI ratio (fmol m2 /mg Kg) were found (p = ns), (Figure 4). The Bmax/BMI ratio was: 39.12 ± 3.11 (min.-max: 9.33-74.80) in men and 36.53 ± 2.21 (min.-max:7.92-87.06) in women. No significant variation was reported in SERT affinity (KD) among the BMI based groups (Figures 1b and 2b).

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