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Updated: May 1, 2026
A Murine Model of Vertical Sleeve Gastrectomy
Published on: December 18, 2017
FXR is a molecular target for the effects of vertical sleeve gastrectomy
Karen K Ryan1, Valentina Tremaroli2, Christoffer Clemmensen3
1Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, Ohio 45237, USA.
Abstract:
Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.
Insights
Vertical sleeve gastrectomy (VSG) effectively treats obesity and type-2 diabetes by altering bile acids and gut microbes. The farnesoid-X receptor (FXR) is crucial for these metabolic benefits, not just stomach restriction.
Area of Science:
- Metabolic surgery
- Obesity research
- Endocrinology
Background:
- Bariatric surgery, including vertical sleeve gastrectomy (VSG), is highly effective for obesity and type-2 diabetes.
- The molecular mechanisms behind VSG's benefits are not fully understood.
- VSG significantly alters circulating bile acids, which regulate metabolism via the farnesoid-X receptor (FXR).
Purpose of the Study:
- To investigate the role of FXR in the therapeutic effects of VSG.
- To determine if VSG's benefits are due to mechanical restriction or metabolic changes.
- To explore the link between bile acids, FXR signaling, and VSG outcomes.
Main Methods:
- VSG surgery was performed on mice with diet-induced obesity.
- Mice with targeted genetic disruption of FXR were studied.
- Changes in body weight, glucose tolerance, bile acid levels, and gut microbiota were analyzed.
Main Results:
- VSG's therapeutic effects are not solely due to mechanical stomach restriction.
- VSG increased circulating bile acids and altered gut microbial communities.
- The beneficial effects of VSG on weight and glucose tolerance were significantly reduced in mice lacking FXR.
Conclusions:
- Bile acid alterations and FXR signaling are key molecular mechanisms underlying VSG's benefits.
- VSG's effectiveness in treating obesity and type-2 diabetes involves FXR-mediated metabolic pathways.
- Targeting bile acid-FXR pathways could offer new therapeutic strategies for metabolic disorders.
