Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids

The Journal of Biological Chemistry
C J SinalF J Gonzalez

Abstract

The peroxisome proliferator-activated receptor-alpha (PPARalpha) is a ligand-activated transcription factor that regulates the expression of a number of genes critical for fatty acid beta-oxidation. Because a number of substrates and intermediates of this metabolic pathway serve as ligand activators of this receptor, homeostatic control of fatty acid metabolism is achieved. Evidence also exists for PPARalpha-dependent regulation of genes encoding critical enzymes of bile acid biosynthesis. To determine whether the primary products of bile acid biosynthesis, cholic acid and chenodeoxycholic acid, were capable of modulating PPARalpha function, a variety of in vivo and in vitro approaches were utilized. Feeding a bile acid-enriched diet significantly reduced the degree of hepatomegaly and induction of target genes encoding enzymes of fatty acid beta-oxidation caused by treatment with the potent PPARalpha ligand Wyeth-14,643. Convergent data from mechanistic studies indicate that bile acids interfere with transactivation by PPARalpha at least in part by impairing the recruitment of transcriptional coactivators. The results of this study provide the first evidence in favor of the existence of compounds, normally found within the bod...Continue Reading

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M GöttlicherJ A Gustafsson
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·B ZhangJ P Capone
Jan 1, 1995·Annual Review of Pharmacology and Toxicology·B G Lake
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·H KellerW Wahli
Sep 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E F JohnsonM H Hsu
Dec 27, 1996·Annals of the New York Academy of Sciences·B M FormanR M Evans
Jan 17, 1997·The Journal of Biological Chemistry·P DowellM Leid
Feb 7, 1997·The Journal of Biological Chemistry·J M LehmannT M Willson
Dec 31, 1997·Molecular and Cellular Biology·W SeolD D Moore
Jan 31, 1998·The Journal of Biological Chemistry·P DowellM Leid
Feb 27, 1998·Frontiers in Bioscience : a Journal and Virtual Library·J Y Chiang
Apr 13, 1999·Gastroenterology Clinics of North America·Z R VlahcevicR T Stravitz
May 21, 1999·Science·M MakishimaB Shan
May 21, 1999·Science·D J ParksJ M Lehmann
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·J L OberfieldT M Willson
Jun 8, 1999·The Journal of Clinical Investigation·S KerstenW Wahli
Jun 9, 1999·Molecular Cell·H WangB M Forman
Aug 17, 1999·Annual Review of Nutrition·D B Jump, S D Clarke
Dec 22, 1999·Current Opinion in Biotechnology·L Michalik, W Wahli
Apr 25, 2000·Clinical Chemistry and Laboratory Medicine : CCLM·P GervoisB Staels
Jun 6, 2000·Nature·S KerstenW Wahli

❮ Previous
Next ❯

Citations

Feb 21, 2003·Biochemical and Biophysical Research Communications·Michung YoonGoo Taeg Oh
Feb 8, 2006·Annual Review of Physiology·Nada Y Kalaany, David J Mangelsdorf
Sep 13, 2006·Environmental Health Perspectives·Nagalakshmi Keshava, Jane C Caldwell
Oct 7, 2008·World Journal of Gastroenterology : WJG·Olga Martinez-Augustin, Fermin Sanchez de Medina
Jul 29, 2009·PPAR Research·Tiangang Li, John Y L Chiang
Nov 5, 2003·Journal of Cellular and Molecular Medicine·N LatruffeM Cherkaoui Malki
May 18, 2004·The Journal of Clinical Investigation·Mitsuhiro WatanabeJohan Auwerx
May 8, 2004·Metabolism: Clinical and Experimental·Sunhyo JeongMichung Yoon
Apr 29, 2005·Journal of Pharmaceutical Sciences·Rommel G Tirona, Richard B Kim
Jun 15, 2007·Toxicologic Pathology·Courtney G WoodsIvan Rusyn
Dec 6, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Suzanne LindBo Angelin
Feb 14, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Sabine M PostHans M G Princen
Apr 13, 2005·The Journal of Biological Chemistry·Tanya C McCarthyChristopher J Sinal
Jun 30, 2011·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Vyacheslav U BukoHorst-Dietmar Tauschel
May 23, 2015·Journal of the Science of Food and Agriculture·Agnes M RimandoWallace Yokoyama
Mar 14, 2017·The Journal of Clinical Investigation·Geoffrey A PreidisDavid D Moore
Jun 27, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hui Yun Penny OhWalter Wahli
Oct 12, 2018·Frontiers of Medicine·Cynthia Rajani, Wei Jia
Feb 20, 2013·Molecular and Cellular Biochemistry·Tao HanCuimei Yuan
Mar 28, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Katrin Panzitt, Martin Wagner
Sep 18, 2004·Metabolism: Clinical and Experimental·Sunhyo JeongMichung Yoon
Nov 22, 2005·Biochemical and Biophysical Research Communications·Hyunghee LeeMichung Yoon
Jun 30, 2006·Molecular and Cellular Endocrinology·Kimihiko MatsusueFrank J Gonzalez

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.