Department of Animal Sciences, University of Florida, Gainesville, FL 32608, USA.
Department of Animal Sciences, University of Florida, Gainesville, FL 32608, USA.
Domest Anim Endocrinol. 2021 Jan;74:106519. doi: 10.1016/j.domaniend.2020.106519. Epub 2020 Jul 9.
Peripheral serotonin regulates energy metabolism in several mammalian species, however, the potential contribution of serotonergic mechanisms as metabolic and endocrine regulators in growing dairy calves remain unexplored. Objectives were to characterize the role of serotonin in glucose and insulin metabolism in dairy calves with increased serotonin bioavailability. Milk replacer was supplemented with saline, 5-hydroxytryptophan (90 mg/d), or fluoxetine (40 mg/d) for 10-d (n = 8/treatment). Blood was collected daily during supplementation and on days 2, 7, and 14 during withdrawal. Calves were euthanized after 10-d supplementation or 14-d withdrawal periods to harvest liver and pancreas tissue. 5-hydroxytryptophan increased circulating insulin concentrations during the supplementation period, whereas both treatments increased circulating glucose concentration during the withdrawal period. The liver and pancreas of preweaned calves express serotonin factors (ie, TPH1, SERT, and cell surface receptors), indicating their ability to synthesize, uptake, and respond to serotonin. Supplementation of 5-hydroxytryptophan increased hepatic and pancreatic serotonin concentrations. After the withdrawal period, fluoxetine cleared from the pancreas but not liver tissue. Supplementation of 5-hydroxytryptophan upregulated hepatic mRNA expression of serotonin receptors (ie, 5-HTR1B, -1D, -2A, and -2B), and downregulated pancreatic 5-HTR1F mRNA and insulin-related proteins (ie, Akt and pAkt). Fluoxetine-supplemented calves had fewer pancreatic islets per microscopic field with reduced insulin intensity, whereas 5-hydroxytryptophan supplemented calves had increased islet number and area with greater insulin and serotonin and less glucagon intensities. After the 14-d withdrawal of 5-hydroxytryptophan, hepatic mRNA expression of glycolytic and gluconeogenic enzymes were simultaneously downregulated. Improving serotonin bioavailability could serve as a potent regulator of endocrine and metabolic processes in dairy calves.
外周血清素在几种哺乳动物物种中调节能量代谢，然而，血清素机制作为代谢和内分泌调节剂在生长乳牛中的潜在贡献仍未得到探索。本研究的目的是描述增加血清素生物利用度对乳牛葡萄糖和胰岛素代谢的作用。在 10 天的时间里，向代乳中添加盐水、5-羟色氨酸（90mg/d）或氟西汀（40mg/d）（n = 8/处理）。在补充期间每天采集血液，并在撤药期间的第 2、7 和 14 天采集血液。在补充 10 天后或撤药 14 天后，对小牛进行安乐死，以收获肝脏和胰腺组织。5-羟色氨酸在补充期间增加了循环胰岛素浓度，而两种处理都增加了撤药期间的循环葡萄糖浓度。未断奶小牛的肝脏和胰腺表达血清素因子（即 TPH1、SERT 和细胞表面受体），表明它们有合成、摄取和对血清素作出反应的能力。5-羟色氨酸的补充增加了肝和胰腺中的血清素浓度。撤药期后，氟西汀从胰腺中清除，但肝脏组织中未清除。5-羟色氨酸的补充上调了肝脏中 5-羟色胺受体（即 5-HTR1B、-1D、-2A 和 -2B）的 mRNA 表达，并下调了胰腺 5-HTR1F mRNA 和胰岛素相关蛋白（即 Akt 和 pAkt）。补充氟西汀的小牛每个显微镜视野中的胰岛数量减少，胰岛素强度降低，而补充 5-羟色氨酸的小牛胰岛数量增加，胰岛素、血清素增加，而胰高血糖素减少。撤药 5-羟色氨酸 14 天后，糖酵解和糖异生酶的肝 mRNA 表达同时下调。提高血清素生物利用度可以作为乳牛内分泌和代谢过程的有效调节剂。
