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

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 [(3)H]-paroxetine ([(3)H]-Par) binding and [(3)H]-5-HT reuptake measurements from April 1(st) to June 30(th) 2019. RESULTS: The [(3)H]-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, triglycerides, glucose, insulin and leptin, while positively with HDL cholesterol (p<.01). The reduction of 5-HT uptake rate (V(max), pmol//min/10(9)platelets) amongst BMI groups was not statistically significant, but V(max) negatively correlated with leptin and uptake affinity values (p<.05). Besides, [(3)H]-Par affinity values positively correlated with glycaemia and triglycerides, while [(3)H]-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 B(max) 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