Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure
Mitsuhiro Watanabe,Yasushi Horai,Sander M. Houten,Kohkichi Morimoto,Taichi Sugizaki,Eri Arita,Chikage Mataki,Hiroyuki Sato,Yusuke Tanigawara,Kristina Schoonjans,Hiroshi Itoh,Johan Auwerx +11 more
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This paper evaluated the metabolic impact of farnesoid X receptor activation by administering a synthetic FXR agonist (GW4064) to mice in which obesity was induced by a high fat diet.About:
This article is published in Journal of Biological Chemistry.The article was published on 2011-07-29 and is currently open access. It has received 229 citations till now. The article focuses on the topics: Farnesoid X receptor & Bile acid.read more
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Journal Article
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. [Erratum: 2004 Sept. 23, v. 431, no. 7007, p. 485.]
Sung Hee Um,Francesca Frigerio,Mitsuhiro Watanabe,Frédéric Picard,Manel Joaquin,Melanie Sticker,Stefano Fumagalli,Peter R. Allegrini,Sara C. Kozma,Johan Auwerx +9 more
TL;DR: In this article, S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation, but on a high fat diet, levels of glucose and free fatty acids still rise in S6k1-dependent mice, resulting in insulin receptor desensitization.
OtherDOI
Bile Acid Metabolism and Signaling
TL;DR: Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis.
Journal ArticleDOI
FXR is a molecular target for the effects of vertical sleeve gastrectomy
Karen K. Ryan,Valentina Tremaroli,Christoffer Clemmensen,Christoffer Clemmensen,Petia Kovatcheva-Datchary,Andriy Myronovych,Rebekah Karns,Hilary E. Wilson-Pérez,Darleen A. Sandoval,Rohit Kohli,Fredrik Bäckhed,Fredrik Bäckhed,Randy J. Seeley +12 more
TL;DR: It is demonstrated 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, which point to bile acid and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.
Journal ArticleDOI
From NASH to HCC: current concepts and future challenges.
Quentin M. Anstee,Quentin M. Anstee,Helen L. Reeves,Helen L. Reeves,Elena Kotsiliti,Olivier Govaere,Mathias Heikenwalder +6 more
TL;DR: This Review discusses NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity and associated metabolic comorbidities, and the challenges and future directions of research.
Journal ArticleDOI
Bile Acid Signaling in Metabolic Disease and Drug Therapy
Tiangang Li,John Y.L. Chiang +1 more
TL;DR: An interaction of liver bile acids and gut microbiota in the regulation of liver metabolism and potential therapeutic agents for treating metabolic diseases of the liver are revealed.
References
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Journal ArticleDOI
A simple method for the isolation and purification of total lipides from animal tissues.
TL;DR: In this paper, the authors described a simplified version of the method and reported the results of a study of its application to different tissues, including the efficiency of the washing procedure in terms of the removal from tissue lipides of some non-lipide substances of special biochemical interest.
Journal ArticleDOI
Identification of a Nuclear Receptor for Bile Acids
Makoto Makishima,Arthur Y. Okamoto,Joyce J. Repa,Hua Tu,R. Marc Learned,Alvin Luk,Mitchell V. Hull,Kevin D. Lustig,David J. Mangelsdorf,Bei Shan +9 more
TL;DR: Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor, which demonstrates a mechanism by which bile acid transcriptionally regulate their biosynthesis and enterohepatic transport.
Journal ArticleDOI
Bile Acids: Natural Ligands for an Orphan Nuclear Receptor
Derek J. Parks,Steven G. Blanchard,Randy K. Bledsoe,Gyan Chandra,Thomas G. Consler,Steven A. Kliewer,Julie B. Stimmel,Timothy M. Willson,Ann Marie Zavacki,David D. Moore,Jürgen M. Lehmann +10 more
TL;DR: Results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis and modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1.
Journal ArticleDOI
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Mitsuhiro Watanabe,Sander M. Houten,Chikage Mataki,Marcelo A. Christoffolete,Brian W. Kim,Hiroyuki Sato,Nadia Messaddeq,John W. Harney,Osamu Ezaki,Tatsuhiko Kodama,Kristina Schoonjans,Antonio C. Bianco,Johan Auwerx +12 more
TL;DR: It is shown that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin, and indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators.
Journal ArticleDOI
A Regulatory Cascade of the Nuclear Receptors FXR, SHP-1, and LRH-1 Represses Bile Acid Biosynthesis
Bryan Goodwin,Stacey A. Jones,Roger R. Price,Michael A. Watson,D.D. McKee,Linda B. Moore,Cristin M. Galardi,Joan G. Wilson,Michael C. Lewis,Matthew E. Roth,Patrick R. Maloney,Timothy M. Willson,Steven A. Kliewer +12 more
TL;DR: A potent, nonsteroidal FXR ligand is used to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain that provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.
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