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The complex interactions among serotonin, insulin, leptin, and glycolipid metabolic parameters in human obesity

Published online by Cambridge University Press:  14 September 2020

Donatella Marazziti*
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy Saint Camillus International University of Health and Medical Sciences, Rome, Italy Brain Research Foundation Lucca, Italy
Laura Betti
Department of Pharmacy, University of Pisa, Italy
Stefano Baroni
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy
Lionella Palego
Department of Pharmacy, University of Pisa, Italy
Federico Mucci
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Italy
Barbara Carpita
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Italy
Ivan Mirco Cremone
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy
Ferruccio Santini
Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy
Laura Fabbrini
Pharmacology and Pharmacogenetics, University Hospital Unit, University of Pisa, Pisa, Italy
Caterina Pelosini
Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy
Alessandro Marsili
Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy
Enrico Massimetti
ASST, «Servizio Psichiatrico Diagnosi e Cura», Hospital of “Bergamo Ovest”, SSD, Treviglio, Italy
Gino Giannaccini
Department of Pharmacy, University of Pisa, Italy
Liliana Dell’Osso
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy
*Author for correspondence: Donatella Marazziti, MD Email:



To provide evidence to the link between serotonin (5-HT), energy metabolism, and the human obese phenotype, the present study investigated the binding and function of the platelet 5-HT transporter (SERT), in relation to circulating insulin, leptin, and glycolipid metabolic parameters.


Seventy-four drug-free subjects were recruited on the basis of divergent body mass index (BMIs) (16.5-54.8 Kg/m2). All subjects were tested for their blood glycolipid profile together with platelet [3H]-paroxetine ([3H]-Par) binding and [3H]-5-HT reuptake measurements from April 1st to June 30th, 2019.


The [3H]-Par Bmax (fmol/mg proteins) was progressively reduced with increasing BMIs (P < .001), without changes in affinity. Moreover, Bmax was negatively correlated with BMI, waist/hip circumferences (W/HC), triglycerides (TD), glucose, insulin, and leptin, while positively with high-density lipoprotein (HDL) cholesterol (P < .01). The reduction of 5-HT uptake rate (Vmax, pmol/min/109 platelets) among BMI groups was not statistically significant, but Vmax negatively correlated with leptin and uptake affinity values (P < .05). Besides, [3H]-Par affinity values positively correlated with glycemia and TD, while [3H]-5-HT reuptake affinity with glycemia only (P < .05). Finally, these correlations were specific of obese subjects, while, from multiple linear-regression analysis conducted on all subjects, insulin (P = .006) resulting negatively related to Bmax independently from BMI.


Present findings suggest the presence of a possible alteration of insulin/5-HT/leptin axis in obesity, differentially impinging the density, function, and/or affinity of the platelet SERT, as a result of complex appetite/reward-related interactions between the brain, gut, pancreatic islets, and adipose tissue. Furthermore, they support the foremost cooperation of peptides and 5-HT in maintaining energy homeostasis.

Original Research
© The Author(s), 2020. Published by Cambridge University Press

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