Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice
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
Abstract
Significance 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.