FXR is a molecular target for the effects of vertical sleeve gastrectomy
Open accessAbstract
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.
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Changes in the composition and diversity of the gut microbiota have been observed after vertical sleeve gastrectomy and RYGB in mice.
“Recent work has also indicated that the gut microbiota may mediate some of the beneficial effects of bariatric surgery, and changes in the composition and diversity of the gut microbiota have been observed in the short term after RYGB in humans (Furet et al., 2010; Graessler et al., 2013; Kong et al., 2013; Zhang et al., 2009), as well as after vertical sleeve gastrectomy and RYGB in mice (Liou et”
From Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation (2015) · cites this paper as Ryan et al., 2014
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- Authors
- Ryan, K. K., Tremaroli, V., Clemmensen, C., Kovatcheva-Datchary, P., Myronovych, A., Karns, R., Wilson-Pérez, H. E., Sandoval, D. A., Kohli, R., Bäckhed, F., & Seeley, R. J.
- Affiliations
- University of Cincinnati (US)
- University of Gothenburg (SE)
- University of Copenhagen (DK)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Seeley, Randy J.
- ORCID
- Venue
- Nature
- Published
- 2014-03-26
- Volume
- 509
- Issue
- 7499
- Pages
- 183-188
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4016120
- OpenAlex
- W2019441910
- Cited by
- 931
- References
- 55
- Citations by year
- 2026: 22 · 2025: 39 · 2024: 36 · 2023: 51 · 2022: 65 · 2021: 84 · 2020: 90 · 2019: 86 · 2018: 72 · 2017: 102 · 2016: 112 · 2015: 116 · 2014: 56
- FWCI
- 128.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk Fonden (NNF13OC0008163)
- National Institutes of Health (UL1TR001425, UL1TR000077)
- National Heart, Lung, and Blood Institute (R00HL111319, K99HL111319)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK082173, K08DK084310, R01DK093848, P30DK078392)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- sleeve gastrectomy, farnesoid X receptor, bile acids, bariatric surgery, obesity, type 2 diabetes, glucose tolerance, gut microbiota, diet-induced obesity, weight loss, nuclear receptor signaling, FXR knockout mice, hepatic bile acid synthesis, hepatic glucose production, hepatic insulin sensitivity, hepatic lipogenesis
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Body Composition, Cecum, Feeding Behavior, Gastrectomy, Gastric Mucosa, Glucose Tolerance Test, Male, Mice, Inbred C57BL, Obesity, Stomach, Signal Transduction, Weight Loss, Glucose Intolerance, Receptors, Cytoplasmic and Nuclear, Bariatric Surgery, Mice
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