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  • 1
    Publication Date: 1999-05-21
    Description: Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parks, D J -- Blanchard, S G -- Bledsoe, R K -- Chandra, G -- Consler, T G -- Kliewer, S A -- Stimmel, J B -- Willson, T M -- Zavacki, A M -- Moore, D D -- Lehmann, J M -- F32 DK09793/DK/NIDDK NIH HHS/ -- R01 DK53366/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 May 21;284(5418):1365-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334993" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bile Acids and Salts/chemistry/*metabolism/pharmacology ; Carrier Proteins/metabolism ; Cell Line ; Chenodeoxycholic Acid/*metabolism/pharmacology ; Cholesterol/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Deoxycholic Acid/metabolism/pharmacology ; Histone Acetyltransferases ; Homeostasis ; Humans ; Ligands ; Lithocholic Acid/metabolism/pharmacology ; Mice ; Nuclear Receptor Coactivator 1 ; *Organic Anion Transporters, Sodium-Dependent ; Protein Conformation ; Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Structure-Activity Relationship ; *Symporters ; Transcription Factors/chemistry/genetics/*metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-03-26
    Description: Fibroblast growth factor (FGF) 19 is an enterokine synthesized and released when bile acids are taken up into the ileum. We show that FGF19 stimulates hepatic protein and glycogen synthesis but does not induce lipogenesis. The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. Mice lacking FGF15 (the mouse FGF19 ortholog) fail to properly maintain blood concentrations of glucose and normal postprandial amounts of liver glycogen. FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076083/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076083/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kir, Serkan -- Beddow, Sara A -- Samuel, Varman T -- Miller, Paul -- Previs, Stephen F -- Suino-Powell, Kelly -- Xu, H Eric -- Shulman, Gerald I -- Kliewer, Steven A -- Mangelsdorf, David J -- DK40936/DK/NIDDK NIH HHS/ -- DK62434/DK/NIDDK NIH HHS/ -- DK67158/DK/NIDDK NIH HHS/ -- R01 DK040936/DK/NIDDK NIH HHS/ -- R01 DK040936-23/DK/NIDDK NIH HHS/ -- R01 DK067158/DK/NIDDK NIH HHS/ -- R01 DK067158-09/DK/NIDDK NIH HHS/ -- R24 DK085638/DK/NIDDK NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19 DK062434-10/DK/NIDDK NIH HHS/ -- U24 DK059635/DK/NIDDK NIH HHS/ -- U24 DK059635-05/DK/NIDDK NIH HHS/ -- U24 DK076169/DK/NIDDK NIH HHS/ -- U24 DK076169-05/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1621-4. doi: 10.1126/science.1198363.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436455" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Eukaryotic Initiation Factors/metabolism ; Fibroblast Growth Factors/*metabolism/*pharmacology ; Glucose/metabolism ; Glycogen Synthase/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Hep G2 Cells ; Humans ; Insulin/*metabolism/pharmacology ; Liver/drug effects/*metabolism ; Liver Glycogen/*biosynthesis ; MAP Kinase Signaling System ; Male ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; *Protein Biosynthesis ; Proto-Oncogene Proteins c-akt/metabolism ; Ribosomal Protein S6/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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