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

• Published in: CNS spectrums Vol. 27; no. 1; pp. 99 - 108
• Main Authors: Marazziti, Donatella, Betti, Laura, Baroni, Stefano, Palego, Lionella, Mucci, Federico, Carpita, Barbara, Cremone, Ivan Mirco, Santini, Ferruccio, Fabbrini, Laura, Pelosini, Caterina, Marsili, Alessandro, Massimetti, Enrico, Giannaccini, Gino, Dell’Osso, Liliana
• Format: Journal Article
• Language: English
• Published: New York, USA Cambridge University Press 01.02.2022
• Subjects: Adipocytes; Blood platelets; Body mass index; Cholesterol; Drug withdrawal; Drugs; Eating disorders; Endocrinology; Gene expression; Glucose; High density lipoprotein; Hormones; Insulin; Kinases; Mental disorders; Metabolic syndrome; Obesity; Original Research; Overweight; Peptides; Proteins; Serotonin; Signal transduction; Weight control; Italy; Obesity; serotonin; insulin; glycolipid metabolism; serotonin transporter; leptin
• DOI: 10.1017/S1092852920001820
• ISSN: 1092-8529

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.