Donatella Marazziti1,2,3, Laura Betti4, Stefano Baroni1, Lionella Palego4, Federico Mucci1,5, Barbara Carpita1,5, Ivan Mirco Cremone1, Ferruccio Santini6, Laura Fabbrini7, Caterina Pelosini6, Alessandro Marsili6, Enrico Massimetti8, Gino Giannaccini4, Liliana Dell'Osso1. 1. Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy. 2. Saint Camillus International University of Health and Medical Sciences, Rome, Italy. 3. Brain Research Foundation Lucca, Italy. 4. Department of Pharmacy, University of Pisa, Italy. 5. Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Italy. 6. Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy. 7. Pharmacology and Pharmacogenetics, University Hospital Unit, University of Pisa, Pisa, Italy. 8. ASST, «Servizio Psichiatrico Diagnosi e Cura», Hospital of "Bergamo Ovest", SSD, Treviglio, Italy.
Abstract
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 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. 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.
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 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. 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.
Authors: Karen Mei-Ling Tan; Mya-Thway Tint; Narasimhan Kothandaraman; Navin Michael; Suresh Anand Sadananthan; S Sendhil Velan; Marielle V Fortier; Fabian Yap; Kok Hian Tan; Peter D Gluckman; Yap-Seng Chong; Mary F F Chong; Yung Seng Lee; Keith M Godfrey; Johan G Eriksson; David Cameron-Smith Journal: J Clin Endocrinol Metab Date: 2022-05-17 Impact factor: 6.134