FXR is a molecular target for the effects of vertical sleeve gastrectomy
By Karen K Ryan, V. Tremaroli, Christoffer Clemmensen, P. Kovatcheva-Datchary, Andriy Myronovych, Rebekah A. Karns, Hilary E. Wilson-Pérez, D. Sandoval, Rohit Kohli, F. Bäckhed and 1 more. Nature, 2014
893 citations recorded by the source corpus.
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.
Subfields: Pulmonary and Respiratory Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/2e047f2d6440711ee92332ed63d0c3d5e22e5beb
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Citations in the corpus
- Gut Microbiota in Cardiovascular Health and Disease (2017, background): “Some of these molecules have been shown to functionally interact with other endocrine hormones, including ghrelin, leptin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY).(44,45) Others have been reported to stimulate the parasympathetic nervous system, thereby impacting glucose homeostasis an”
- Treatment of Obesity with Celastrol (2015, positive): “The effect of Celastrol is more potent than reported for bariatric surgery in mice, with which weight loss is around 35%–40% (Liou et al., 2013; Mokadem et al., 2014; Ryan et al., 2014).”
- Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation (2015, methodology): “…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 al., 2013; Ryan et al., 2014).”
- Bile Acid Signaling in Metabolic Disease and Drug Therapy (2014, background): “A recent study of vertical sleeve gastrectomy (VSG) in mice showed that increased circulating bile acids after VSG might change gut microbial communities (Ryan et al., 2014).”
- Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease (2020, background): “Metabolic benefits from bariatric surgery, including weight loss and improved glucose metabolism, were absent in mice lacking the TGR5 receptor (705), suggesting an important role for bile acids in the metabolic improvements associated with bariatric surgery.”
- Lipotoxicity and the gut-liver axis in NASH pathogenesis. (2018, background): “It is recognized that these circulating BAs, in addition to the above mentioned functions, can coordinate a wide number of pathways, mediated by specific nuclear receptors (NRs) [134-136].”