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

Objective 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. Methods 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. Results The [3H]-Par B max (fmol/mg proteins) was progressively reduced with increasing BMIs (P .001), without changes in affinity. Moreover, B max 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 (V max, pmol/min/109 platelets) among BMI groups was not statistically significant, but V max 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 B max independently from BMI. Conclusions 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.