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Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice.

ABSTRACT:

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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).

SUBMITTER: Ding L

PROVIDER: S-EPMC4992413 | biostudies-literature |

REPOSITORIES: biostudies-literature

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TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice.

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Transcriptomics analysis of enteroendocrine cells following vertical sleeve gastrectomy

Project description:This SuperSeries is composed of the SubSeries listed below.

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The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation.

Project description:Elevated levels of branched-chain amino acids (BCAAs) and their metabolites are strongly positively associated with obesity, insulin resistance, and type 2 diabetes. Bariatric surgery is among the best treatments for weight loss and associated morbidities. Clinical studies have reported that bariatric surgery decreases the circulating levels of BCAAs. The objective of this study was to test the hypothesis that reduced BCAA levels contribute to the metabolic improvements of sustained weight loss and improved glucose tolerance after vertical sleeve gastrectomy (VSG). We find that, as in humans, circulating BCAAs are significantly lower in VSG rats and mice. To increase circulating BCAAs, we tested mice with either increased dietary intake of BCAAs or impaired BCAA catabolism by total body deletion of mitochondrial phosphatase 2C (Pp2cm). Our results show that a decrease in circulating BCAAs is not necessary for sustained body weight loss and improved glucose tolerance after VSG.

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RNAseq Analysis of Mouse Stomach and Intestines Following Vertical Sleeve Gastrectomy

Project description:Bariatric surgery, an effective treatment for obesity and diabetes, leads to profound remodeling of whole body energy homeostasis. We utilized a mouse model of vertical sleeve gastrectomy (VSG), a common bariatric surgery as a tool to identify novel secreted proteins and peptides that might act as important metabolic regulators. We analyzed gene expression in the stomach and intestines following VSG or sham surgery in diet-induced obese mice and sought to identify differentially regulated genes encoding secreted proteins/peptides.

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Transcriptomics analysis of human jejunal enteroendocrine cells after vertical sleeve gastrectomy

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Sleeve Gastrectomy Improves Glycemia Independent of Weight Loss by Restoring Hepatic Insulin Sensitivity.

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A comparison of rodent models of vertical sleeve gastrectomy.

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