气候变化领域集成服务门户(CCPortal): Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice

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DOI	10.1073/pnas.2019388118
	Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice
	Ding L.; Zhang E.; Yang Q.; Jin L.; Sousa K.M.; Dong B.; Wang Y.; Tu J.; Ma X.; Tian J.; Zhang H.; Fang Z.; Guan A.; Zhang Y.; Wang Z.; Moore D.D.; Yang L.; Huang W.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Bariatric surgery; Bile acids; Cyp27A1; Farnesoid X receptor; Lipid absorption
语种	英语
scopus关键词	bile acid; farnesoid X receptor; oxygenase; taurocholic acid; animal experiment; animal model; animal tissue; Article; bariatric surgery; controlled study; diet supplementation; gene targeting; intestine; lipid absorption; liver; mouse; nonhuman; priority journal; protein expression; sleeve gastrectomy
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180754
作者单位	Shanghai Key Laboratory of Complex Prescriptions, Ministry of Education Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, United States; Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China; Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA 92350, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States; Graduate School of Biological Science, City of Hope National Medical Center, Duarte, CA 91010, United States; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medic...
推荐引用方式 GB/T 7714	Ding L.,Zhang E.,Yang Q.,et al. Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice[J],2021,118(6).
APA	Ding L..,Zhang E..,Yang Q..,Jin L..,Sousa K.M..,...&Huang W..(2021).Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Ding L.,et al."Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).