Serotonin, insulin, leptin and glycolipid metabolic factor’s relationship in obesity

Abstract

Introduction Obesity, defined by an excessive body fat accumulation, is a non-communicable condition attaining epidemic proportions in economically developed countries. Objectives 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, glycolipid metabolic parameters and body-mass indices (BMIs, Kg m-2). Methods The study included an observational clinical cohort of 74 drug-free subjects (51W; 23M), recruited on the basis of divergent BMIs (16.5-54.8 Kg m-2). All subjects were tested for their blood glycolipid profile together platelet [3H]-paroxetine ([3H]-Par) binding and [3H]-5-HT reuptake measurements from April 1st to June 30th 2019. Results 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, triglycerides, glucose, insulin and leptin, while positively with HDL cholesterol (p<.01). The reduction of 5-HT uptake rate (Vmax, pmol//min/109platelets) amongst 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 glycaemia and triglycerides, while [3H]-5-HT reuptake affinity with glycaemia only (p<.05). Finally, these correlations were specific of obese subjects, while, from multivariate linear-regression analysis conducted on all subjects, insulin (p=.006) resulting negatively related to Bmax independently from BMI. Conclusions The present findings would suggest the presence of a dysfunctional insulin/5-HT/leptin axis in obesity, differentially impinging the density, function and/or affinity of the platelet SERT, as the result of complex appetite/reward-related interactions between the brain, gut, pancreatic islets and adipose tissue. In addition, they support the foremost cooperation of insulin and 5-HT in maintaining energy homeostasis. Disclosure of Interest None Declared