餐后代谢组学分析揭示了减肥后低血糖症中紊乱的血清素代谢。

Rafael Ferraz-Bannitz,Berkcan Ozturk,Cameron J Cummings,Vissarion Efthymiou,Pilar Casanova Querol,Lindsay Poulos,Hanna J Wang,Valerie Navarrete,Hamayle Saeed,Christopher M Mulla,Hui Pan,Jonathan M Dreyfuss,Donald C Simonson,Darleen A Sandoval,Mary-Elizabeth Patti
{"title":"餐后代谢组学分析揭示了减肥后低血糖症中紊乱的血清素代谢。","authors":"Rafael Ferraz-Bannitz,Berkcan Ozturk,Cameron J Cummings,Vissarion Efthymiou,Pilar Casanova Querol,Lindsay Poulos,Hanna J Wang,Valerie Navarrete,Hamayle Saeed,Christopher M Mulla,Hui Pan,Jonathan M Dreyfuss,Donald C Simonson,Darleen A Sandoval,Mary-Elizabeth Patti","doi":"10.1172/jci180157","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nBariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1 to 3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin.\r\n\r\nMETHODS\r\nTo identify mediators of disordered metabolism in PBH, we analyzed plasma metabolome in fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-RYGB (n = 10), and non-surgical controls (n = 8).\r\n\r\nRESULTS\r\nIn the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone beta-hydroxybutyrate were increased by 30% to 80% in PBH vs. asymptomatic. Conversely, multiple amino acids (BCAA, tryptophan) and polyunsaturated lipids were reduced by 20% to 50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced by 2- to 10-fold in PBH in fasting state. Postprandially, plasma serotonin was uniquely increased by 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin.\r\n\r\nCONCLUSION\r\nTogether these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target.\r\n\r\nFUNDING\r\nNIH grant R01 DK121995, NIH grant P30 DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP grant 2018/22111-2.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia.\",\"authors\":\"Rafael Ferraz-Bannitz,Berkcan Ozturk,Cameron J Cummings,Vissarion Efthymiou,Pilar Casanova Querol,Lindsay Poulos,Hanna J Wang,Valerie Navarrete,Hamayle Saeed,Christopher M Mulla,Hui Pan,Jonathan M Dreyfuss,Donald C Simonson,Darleen A Sandoval,Mary-Elizabeth Patti\",\"doi\":\"10.1172/jci180157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND\\r\\nBariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1 to 3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin.\\r\\n\\r\\nMETHODS\\r\\nTo identify mediators of disordered metabolism in PBH, we analyzed plasma metabolome in fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-RYGB (n = 10), and non-surgical controls (n = 8).\\r\\n\\r\\nRESULTS\\r\\nIn the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone beta-hydroxybutyrate were increased by 30% to 80% in PBH vs. asymptomatic. Conversely, multiple amino acids (BCAA, tryptophan) and polyunsaturated lipids were reduced by 20% to 50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced by 2- to 10-fold in PBH in fasting state. Postprandially, plasma serotonin was uniquely increased by 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin.\\r\\n\\r\\nCONCLUSION\\r\\nTogether these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target.\\r\\n\\r\\nFUNDING\\r\\nNIH grant R01 DK121995, NIH grant P30 DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP grant 2018/22111-2.\",\"PeriodicalId\":520097,\"journal\":{\"name\":\"The Journal of Clinical Investigation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Clinical Investigation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1172/jci180157\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Clinical Investigation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1172/jci180157","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

背景减肥手术是治疗肥胖症和 2 型糖尿病的有效方法,但可能会因减肥后低血糖症(PBH)而变得复杂。为了确定 PBH 代谢紊乱的介质,我们分析了空腹状态、混合餐后 30 分钟和 120 分钟 3 组患者的血浆代谢组:结果在空腹状态下,PBH 与无症状者相比,多种三羧酸循环中间产物和酮β-羟基丁酸增加了 30% 至 80%。相反,PBH 与无症状者相比,多种氨基酸(BCAA、色氨酸)和多不饱和脂质减少了 20% 至 50%。色氨酸相关代谢物,包括犬尿酸盐、黄尿酸盐和血清素,在空腹状态下减少了 2 到 10 倍。餐后,PBH 与无症状的 RYGB 术后患者相比,血浆中的血清素独特地增加了 1.9 倍。在小鼠体内,5-羟色胺可降低血糖,增加血浆胰岛素和 GLP-1。此外,非特异性血清素受体拮抗剂环丙沙星和特异性血清素受体 2 拮抗剂酮塞林可阻断血清素诱导的小鼠低血糖。资助美国国立卫生研究院资助R01 DK121995、美国国立卫生研究院资助P30 DK036836(糖尿病研究中心资助,乔斯林糖尿病中心)和圣保罗州研究基金资助2018/22111-2。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia.
BACKGROUND Bariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1 to 3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin. METHODS To identify mediators of disordered metabolism in PBH, we analyzed plasma metabolome in fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-RYGB (n = 10), and non-surgical controls (n = 8). RESULTS In the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone beta-hydroxybutyrate were increased by 30% to 80% in PBH vs. asymptomatic. Conversely, multiple amino acids (BCAA, tryptophan) and polyunsaturated lipids were reduced by 20% to 50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced by 2- to 10-fold in PBH in fasting state. Postprandially, plasma serotonin was uniquely increased by 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin. CONCLUSION Together these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target. FUNDING NIH grant R01 DK121995, NIH grant P30 DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP grant 2018/22111-2.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信