ObjectiveTo 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.MethodsSeventy-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.ResultsThe [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.ConclusionsPresent 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.

中文翻译：

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血清素、胰岛素、瘦素和糖脂代谢参数在人类肥胖症中的复杂相互作用

目的为提供血清素 (5-HT)、能量代谢和人类肥胖表型之间联系的证据，本研究调查了血小板 5-HT 转运蛋白 (SERT) 与循环胰岛素、瘦素、方法根据不同的体重指数（BMIs）（16.5-54.8 Kg/m）招募74名无药物受试者2）。对所有受试者的血液糖脂谱和血小板进行了测试[3H]-帕罗西汀（[3H]-Par) 绑定和 [3H]-5-HT 再摄取测量时间为 2019 年 4 月 1 日至 6 月 30 日。结果 [3H]-Par乙最大限度（fmol/mg 蛋白质）随着 BMI 的增加而逐渐降低（磷< .001)，亲和力不变。而且，乙最大限度与 BMI、腰/臀围 (W/HC)、甘油三酯 (TD)、葡萄糖、胰岛素和瘦素呈负相关，而与高密度脂蛋白 (HDL) 胆固醇呈正相关。磷< .01)。5-HT 摄取率的降低 (五最大限度, pmol/min/109BMI 组之间的血小板）无统计学意义，但五最大限度与瘦素和摄取亲和力值负相关（磷< .05)。除了， [3H]-Par 亲和力值与血糖和 TD 呈正相关，而 [3H]-5-HT 再摄取亲和力仅与血糖有关 (磷< .05)。最后，这些相关性是肥胖受试者特有的，而根据对所有受试者进行的多重线性回归分析，胰岛素（磷= .006) 产生负相关乙最大限度独立于 BMI。结论目前的研究结果表明，肥胖中存在胰岛素/5-HT/瘦素轴的可能改变，不同地影响血小板 SERT 的密度、功能和/或亲和力，这是由于复杂的食欲/奖励-大脑、肠道、胰岛和脂肪组织之间的相关相互作用。此外，它们支持肽和 5-HT 在维持能量稳态方面的最重要的合作。