Vertical Sleeve Gastrectomy Confers Metabolic Improvements by Reducing Intestinal Bile Acids and Lipid Absorption in Mice

Authors

Lili Ding
Eryun Zhang
Qiaoling Yang
Lihua Jin
Kyle M Sousa
Bingning Dong
Yangmeng Wang
Jui Tu
Xiaoxiao Ma
Jingyan Tian
Hongli Zhang
Zhipeng Fang
Ana Guan
Yixin Zhang
Zhengtao Wang
David D Moore
Li Yang
Wendong Huang

Publication Date

2-9-2021

Journal

Proceedings of the National Academy of Sciences of the United States of America

DOI

10.1073/pnas.2019388118

PMID

33526687

PMCID

PMC8017941

PubMedCentral® Posted Date

2-1-2021

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Animals, Bile Acids and Salts, Cholestanetriol 26-Monooxygenase, Diet, High-Fat, Gastrectomy, Humans, Lipid Metabolism, Lipids, Mice, Mice, Knockout, Obesity, Morbid, Receptors, Cytoplasmic and Nuclear, Weight Loss, bile acids, bariatric surgery, farnesoid X receptor, cyp27a1, lipid absorption

Abstract

Vertical sleeve gastrectomy (VSG) is a highly effective bariatric surgery that sustainably treats obesity and type 2 diabetes (T2D). However, the underlying mechanisms governing its metabolic benefits remain unclear. In this study, we have used four different genetically modified mouse lines to understand the link between bile acid circulation and metabolic effects of VSG. Instead of directly activating the nuclear bile acid receptor farnesoid X receptor (Fxr) in the liver or intestine, VSG reduces intestinal levels of bile acids, thereby decreasing fat absorption in the intestine. Given the rising popularity of bariatric surgeries to treat obesity and associated T2D, the results described herein provide mechanistic insights that may lead to safer noninvasive approaches to mimic the metabolic effects of bariatric surgery.

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