Journal ArticleDOI
Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease.
Sunder Mudaliar,Robert R. Henry,Arun J. Sanyal,Linda Morrow,Hanns-Ulrich Marschall,Mark Kipnes,Luciano Adorini,Cathi Sciacca,Paul Clopton,E. Castelloe,Paul Dillon,Mark Pruzanski,David Shapiro +12 more
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TLDR
Administration of 25 or 50 mg OCA for 6 weeks was well tolerated, increased insulin sensitivity, and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease.About:
This article is published in Gastroenterology.The article was published on 2013-09-01. It has received 794 citations till now. The article focuses on the topics: Insulin resistance & Nonalcoholic fatty liver disease.read more
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Journal ArticleDOI
Mouse species-specific control of hepatocarcinogenesis and metabolism by FGF19/FGF15.
TL;DR: Fundamental species-associated differences between FGF19 and FGF15 may restrict the relevance of mouse models for the study of the FXR/FGF19 pathway, and underscore the importance of clinical assessment of this pathway, with respect to both safety and efficacy in humans.
Journal ArticleDOI
Interaction of gut microbiota with dysregulation of bile acids in the pathogenesis of nonalcoholic fatty liver disease and potential therapeutic implications of probiotics
TL;DR: It is posited that microbiome restoration could be an alternative approach for the treatment of NAFLD and careful selection of commensal bacteria for probiotics may lead to an effective therapy forNAFLD.
Journal ArticleDOI
Progress and challenges of selective Farnesoid X Receptor modulation.
Vittoria Massafra,Roberto Pellicciari,Antimo Gioiello,Saskia W.C. van Mil,Saskia W.C. van Mil +4 more
TL;DR: The rationale for the design of SBARMs comprising dissociation between metabolic and inflammatory signaling, gene-selective and tissue-specific targeting, and the potential structural mechanisms underlying the binding properties of dissociating ligands of FXR are reviewed.
Journal ArticleDOI
Bile Acids and FXR: Novel Targets for Liver Diseases.
TL;DR: An updated literature review on BA homeostasis and FXR modulator development is provided and it is shown that FXR plays a tissue-specific role in suppressing BA synthesis and promoting BA enterohepatic circulation.
Journal ArticleDOI
Targeting Metabolism, Insulin Resistance, and Diabetes to Treat Nonalcoholic Steatohepatitis.
TL;DR: This Perspective will review some of the relevant literature on the topic and examine approved and experimental NASH therapeutic concepts that target intermediary metabolism, insulin resistance, and diabetes to treat this emerging public health problem.
References
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Journal ArticleDOI
Diagnosis and Classification of Diabetes Mellitus
TL;DR: The chronic hyperglycemia of diabetes is associated with long-term damage, dys-function, and failure of differentorgans, especially the eyes, kidneys, nerves, heart, and blood vessels.
Journal ArticleDOI
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
TL;DR: Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique] are described.
Journal ArticleDOI
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Takeshi Inagaki,Mihwa Choi,Antonio Moschetta,Li Peng,Carolyn L. Cummins,Jeffrey G. McDonald,Guizhen Luo,Stacey A. Jones,Bryan Goodwin,James A. Richardson,Robert D. Gerard,Joyce J. Repa,David J. Mangelsdorf,Steven A. Kliewer +13 more
TL;DR: It is demonstrated that fibroblast growth factor 15 signals from intestine to liver to repress the gene encoding cholesterol 7alpha-hydroxylase (CYP7A1), which catalyzes the first and rate-limiting step in the classical bile acid synthetic pathway.
Journal ArticleDOI
Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.
Sama I. Sayin,Annika Wahlström,Jenny Felin,Sirkku Jäntti,Hanns-Ulrich Marschall,Krister Bamberg,Bo Angelin,Tuulia Hyötyläinen,Matej Orešič,Fredrik Bäckhed,Fredrik Bäckhed +10 more
TL;DR: It is suggested that the gut microbiota not only regulates secondary bile acids metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.
Journal ArticleDOI
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
TL;DR: Results suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes.
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Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial
Brent A. Neuschwander-Tetri,Rohit Loomba,Arun J. Sanyal,Joel E. Lavine,Mark L. Van Natta,Manal F. Abdelmalek,Naga Chalasani,Srinivasan Dasarathy,Anna Mae Diehl,Bilal Hameed,Kris V. Kowdley,Arthur J. McCullough,Norah A. Terrault,Jeanne M. Clark,James Tonascia,Elizabeth M. Brunt,David E. Kleiner,Edward Doo +17 more