1. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice
- Author
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Ricardo Ramirez, Qiaoling Yang, Dustin Schones, Ying Gu, Byung-Wook Kim, Zhenzhou Xiao, Donna Yu, David D. Moore, Lili Ding, Zhengtao Wang, Jie Wang, Alessio Pigazzi, Wendong Huang, Bingning Dong, Kyle M. Sousa, Lihua Jin, and Li Yang
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Sleeve gastrectomy ,medicine.medical_treatment ,Adipose tissue ,030209 endocrinology & metabolism ,Biology ,Article ,Receptors, G-Protein-Coupled ,Bile Acids and Salts ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Adipose Tissue, Brown ,Gastrectomy ,Ileum ,Internal medicine ,Diabetes mellitus ,parasitic diseases ,Weight Loss ,medicine ,Animals ,Receptor ,Mice, Knockout ,Hepatology ,Fatty liver ,medicine.disease ,G protein-coupled bile acid receptor ,3. Good health ,Fatty Liver ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Insulin Resistance ,Energy Metabolism - Abstract
Vertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries used for the remission of obesity and diabetes. However, the precise molecular mechanism by which VSG exerts its beneficial effects remains elusive. We report that the membrane-bound G protein-coupled bile acid receptor, GPBAR-1 (also known as TGR5), is required to mediate the effects of anti-obesity, anti-hyperglycemia, and improvements of fatty liver of VSG in mice. In the absence of TGR5, the beneficial metabolic effects of VSG in mice are lost. Moreover, we found that the expression of TGR5 increased significantly after VSG, and VSG alters both BA levels and composition in mice, resulting in enhancement of TGR5 signaling in the ileum and brown adipose tissues, concomitant with improved glucose control and increased energy expenditure. Conclusion: Our study elucidates a novel underlying mechanism by which VSG achieves its postoperative therapeutic effects through enhanced TGR5 signaling. (Hepatology 2016;64:760-773)
- Published
- 2016