1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1016/j.molmet.2018.01.005" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.molmet.2018.01.005</a> Rights Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). Pages 131-140 Volume 9 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR. Publisher An entity responsible for making the resource available Molecular metabolism Date A point or period of time associated with an event in the lifecycle of the resource 2018 2018-03 Subject The topic of the resource Humans; Male; Animals; Mice; *Atherosclerosis; *Farnesoid X receptor; *NAFLD; *Obesity; *TGR5; Diet; Hep G2 Cells; Receptors; Inbred C57BL; High-Fat/adverse effects; Cytoplasmic and Nuclear/*agonists; Bile Acids and Salts/pharmacology/*therapeutic use; Hypercholesterolemia/*drug therapy/etiology/metabolism; Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism; Obesity/*drug therapy/etiology/metabolism; G-Protein-Coupled/*agonists Creator An entity primarily responsible for making the resource Jadhav Kavita; Xu Yang; Xu Yanyong; Li Yuanyuan; Xu Jiesi; Zhu Yingdong; Adorini Luciano; Lee Yoon Kwang; Kasumov Takhar; Yin Liya; Zhang Yanqiao Description An account of the resource OBJECTIVES: Activation of the bile acid (BA) receptors farnesoid X receptor (FXR) or G protein-coupled bile acid receptor (GPBAR1; TGR5) improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. METHODS: Wild-type (WT), Tgr5(-/-), Fxr(-/-), Apoe(-/-) and Shp(-/-) mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. RESULTS: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (CEBPalpha) as novel Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1016/j.molmet.2018.01.005" target="_blank" rel="noreferrer noopener">10.1016/j.molmet.2018.01.005</a> *Atherosclerosis *Farnesoid X receptor *NAFLD *Obesity *TGR5 2018 Adorini Luciano Animals Bile Acids and Salts/pharmacology/*therapeutic use Cytoplasmic and Nuclear/*agonists Department of Integrative Medical Sciences Department of Pharmaceutical Sciences Diet G-Protein-Coupled/*agonists Hep G2 Cells High-Fat/adverse effects Humans Hypercholesterolemia/*drug therapy/etiology/metabolism Inbred C57BL Jadhav Kavita Kasumov Takhar Lee Yoon Kwang Li Yuanyuan Male Mice Molecular metabolism NEOMED College of Medicine NEOMED College of Pharmacy Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism Obesity/*drug therapy/etiology/metabolism Receptors Xu Jiesi Xu Yang Xu Yanyong Yin Liya Zhang Yanqiao Zhu Yingdong