Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the marine small intestine

Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the marine small intestine
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DOI:
10.1016/j.jpedsurg.2019.02.027
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发表时间:
2019-06-01
影响因子:
2.4
通讯作者:
Cowles, Robert A.
Cowles, Robert A.
中科院分区:
医学3区
文献类型:
--
作者:
Park, Christine J.;Armenia, Sarah J.;Cowles, Robert A.

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背景:肠血清素影响肠道内环境稳定,并作为一种粘膜生长因子发挥作用。以前,我们证明了增加粘膜表面积和增强隐窝细胞增殖5-羟色胺再摄取转运蛋白(SERT)缺陷小鼠。材料和方法:将野生型C57 BI/6(WT)和SERT敲除(SERTKO)小鼠禁食,然后用D-木糖或硼-二吡咯亚甲基(BODIPY)IL-C12中链脂肪酸类似物管饲。在灌胃后30 ~ 360 min连续测定血清D-木糖和BODIPY浓度,并从两组中收集小肠用于形态计量学参数的比较。计算曲线下的面积,并将平均值与Student's t检验进行比较,p <0.05。结果:与WT相比,SERTKO动物的小肠中端和远端的绒毛高度和隐窝深度显著更大。与WT动物相比,SERTKO动物中D-木糖和BODIPY的总体吸收更大。D-木糖的吸收持续升高SERTKO动物,而BODIPY的吸收有一个最初的延迟,随后由一个持续的和显着更大的吸收SERTKO动物在60-360分钟后gavage.Conclusion:增强SERTKO小鼠的5-羟色胺信号导致小肠粘膜生长和增强体内碳水化合物和脂肪的吸收。这些功能性增加支持靶向5-羟色胺信号传导系统的概念,以增强肠衰竭背景下的肠适应性。(C)2019爱思唯尔公司All rights reserved.
Background: Enteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid absorption.Material and methods: Wild-type C57BI/6 (WT) and SERT-knockout (SERTKO) mice were fasted then gavaged with D-xylose or boron-dipyrromethene (BODIPY) IL-C12 medium-chain fatty acid analog. Serum D-xylose and BODIPY concentrations were serially measured from blood drawn at 30 to 360 min post-gavage.Small intestine was harvested from both groups for comparison of morphometric parameters. Area under the curve of plotted graphs was calculated, and means were compared with Student's t-test to a significance of p < 0.05.Results: Villus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60-360 min after gavage.Conclusion: Potentiation of serotonin signaling in SERTKO mice results in small intestinal mucosal growth and enhanced carbohydrate and fat absorption in vivo. These functional increases support the concept of targeting the serotonin signaling system to augment intestinal adaptation in the setting of intestinal failure. (C) 2019 Elsevier Inc. All rights reserved.