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BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid.pdf Public Deposited

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https://ir.library.oregonstate.edu/concern/articles/hx11xh11w

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  • The farnesoid X receptor (FXR) regulates bile acid, lipid and glucose metabolism. Here we show that treatment of mice with glycine-b-muricholic acid (Gly-MCA) inhibits FXR signalling exclusively in intestine, and improves metabolic parameters in mouse models of obesity. Gly-MCA is a selective high-affinity FXR inhibitor that can be administered orally and prevents, or reverses, high-fat diet-induced and genetic obesity, insulin resistance and hepatic steatosis in mice. The high-affinity FXR agonist GW4064 blocks Gly-MCA action in the gut, and intestine-specific Fxr-null mice are unresponsive to the beneficial effects of Gly-MCA. Mechanistically, the metabolic improvements with Gly-MCA depend on reduced biosynthesis of intestinal-derived ceramides, which directly compromise beige fat thermogenic function. Consequently, ceramide treatment reverses the action of Gly-MCA in high-fat diet-induced obese mice. We further show that FXR signalling in ileum biopsies of humans positively correlates with body mass index. These data suggest that Gly-MCA may be a candidate for the treatment of metabolic disorders.
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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-12-16T21:57:37Z (GMT) No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid.pdf: 2888956 bytes, checksum: 0ca708562126043797b8109fdbed8e52 (MD5) BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid(Supplementary Figures 1-17, Supplementary Tables 1-3 and Supplementary Reference).pdf: 16936805 bytes, checksum: 7877fdd521ba22c062faf91763311ee6 (MD5)
  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-12-16T21:57:18Z No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid.pdf: 2888956 bytes, checksum: 0ca708562126043797b8109fdbed8e52 (MD5) BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid(Supplementary Figures 1-17, Supplementary Tables 1-3 and Supplementary Reference).pdf: 16936805 bytes, checksum: 7877fdd521ba22c062faf91763311ee6 (MD5)
  • description.provenance : Made available in DSpace on 2015-12-16T21:57:37Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid.pdf: 2888956 bytes, checksum: 0ca708562126043797b8109fdbed8e52 (MD5) BissonWilliamEnvironMoleToxIntestineSelectiveFarnesoid(Supplementary Figures 1-17, Supplementary Tables 1-3 and Supplementary Reference).pdf: 16936805 bytes, checksum: 7877fdd521ba22c062faf91763311ee6 (MD5) Previous issue date: 2015-12-15

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