Transgenic expression of cholesterol 7alpha-hydroxylase in the liver prevents high-fat diet-induced obesity and insulin resistance in mice.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Tiangang LiJohn Y L Chiang

Abstract

Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway that converts cholesterol into bile acids in the liver. Recent studies have shown that bile acids may play an important role in maintaining lipid, glucose, and energy homeostasis. However, the role of CYP7A1 in the development of obesity and diabetes is currently unclear. In this study, we demonstrated that transgenic mice overexpressing Cyp7a1 in the liver [i.e., Cyp7a1 transgenic (Cyp7a1-tg) mice] were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and insulin resistance. Cyp7a1-tg mice showed increased hepatic cholesterol catabolism and an increased bile acid pool. Cyp7a1-tg mice had increased secretion of hepatic very low density lipoprotein but maintained plasma triglyceride homeostasis. Gene expression analysis showed that the hepatic messenger RNA expression levels of several critical lipogenic and gluconeogenic genes were significantly decreased in HFD-fed Cyp7a1-tg mice. HFD-fed Cyp7a1-tg mice had increased whole body energy expenditure and induction of fatty acid oxidation genes in the brown adipose tissue. This study shows that Cyp7a1 plays a critical role in maintaining whole body lipid, glucose,...Continue Reading

References

Jan 15, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Jon H MiyakeRoger A Davis
Jul 3, 2002·The Journal of Clinical Investigation·Clive R PullingerJohn P Kane
May 18, 2004·The Journal of Clinical Investigation·Mitsuhiro WatanabeJohan Auwerx
Mar 2, 2005·Nature Reviews. Molecular Cell Biology·Stefan KraussBradford B Lowell
Jul 5, 2005·Journal of Lipid Research·Marnie L GruenAlyssa H Hasty
Jan 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yanqiao ZhangPeter A Edwards
Feb 1, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Geoffrey C Farrell, Claire Z Larter
Feb 8, 2006·Annual Review of Physiology·Sudha B Biddinger, C Ronald Kahn
Jun 17, 2006·Diabetes, Obesity & Metabolism·Sherwyn L Schwartz
Sep 8, 2006·Journal of Lipid Research·Karen E MatsukumaTimothy F Osborne
Aug 2, 2008·Nature Reviews. Drug Discovery·Charles ThomasKristina Schoonjans
Jan 8, 2009·Physiological Reviews·Philippe LefebvreBart Staels
Apr 7, 2009·Journal of Lipid Research·John Y L Chiang
Apr 10, 2009·The New England Journal of Medicine·Aaron M CypessC Ronald Kahn
Sep 3, 2009·Cell Metabolism·Charles ThomasKristina Schoonjans

❮ Previous
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Citations

Mar 25, 2011·Current Diabetes Reports·Janne PrawittBart Staels
Dec 2, 2010·Nature Reviews. Gastroenterology & Hepatology·Lionel Hebbard, Jacob George
Mar 15, 2012·Nature Reviews. Molecular Cell Biology·Anna C Calkin, Peter Tontonoz
Dec 7, 2011·The Journal of Biological Chemistry·Tiangang LiJohn Y L Chiang
Jun 12, 2013·Metabolic Syndrome and Related Disorders·Giovanni TargherChristopher D Byrne
Sep 7, 2013·Science·Vanessa K RidauraJeffrey I Gordon
May 26, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ryan D JonesStephen D Turley
Oct 13, 2011·Journal of Lipids·Tiangang Li, John Y L Chiang
Nov 14, 2013·Nutrition & Metabolism·Shinichi MeguroTadashi Hase
Jul 3, 2013·Biological & Pharmaceutical Bulletin·Rosa Mistica Coles IgnacioKyu-Jae Lee
Mar 29, 2014·Cholesterol·Joshua S WootenRon C Hoogeveen
Aug 21, 2014·Biochimica Et Biophysica Acta·Raffaella Maria GadaletaAntonio Moschetta
Dec 30, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Georgy HartmannKaushik Mitra
Apr 12, 2011·Expert Review of Gastroenterology & Hepatology·Samuele De Minicis, Gianluca Svegliati-Baroni
Mar 22, 2012·Expert Opinion on Drug Metabolism & Toxicology·Lisa M Younk, Stephen N Davis
Oct 24, 2014·Diabetes·Achint KaurMichael R Hayden
Dec 27, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Bryan L Copple, Tiangang Li
May 28, 2015·Diabetes·Ele FerranniniRebecca A Haeusler
Dec 29, 2015·Clinical and Experimental Pharmacology & Physiology·Shigeru MurakamiNobuhiro Fukuda
Nov 14, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Joan Carles Escolà-GilFrancisco Blanco-Vaca
Nov 19, 2015·Acta Pharmaceutica Sinica. B·Eric KwongHuiping Zhou
Aug 14, 2012·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Chiara GabbiNicola Carulli
Dec 17, 2015·Nature Communications·Changtao JiangFrank J Gonzalez
Jul 17, 2015·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·R StinkensE E Blaak
Mar 10, 2015·Journal of Hepatology·Frank J GonzalezAndrew D Patterson
Feb 15, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tiangang LiJohn Y L Chiang
Mar 29, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tiangang LiJohn Y L Chiang
Jan 10, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lars P BechmannAli Canbay
Jun 2, 2015·Gastroenterology·Willscott E NauglerMarkus Grompe
Sep 10, 2014·Best Practice & Research. Clinical Gastroenterology·Huijuan Ma, Mary Elizabeth Patti
Jan 18, 2011·Journal of Hepatology·Andreas Geier
Dec 17, 2014·Frontiers in Physiology·Brian E SansburyBradford G Hill
Dec 17, 2014·The Journal of Clinical Investigation·Changtao JiangFrank J Gonzalez
Jun 12, 2016·Trends in Molecular Medicine·Owein Guillemot-LegrisGiulio G Muccioli

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