PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation

The American Journal of Pathology
Qian GaoJanardan K Reddy

Abstract

Obesity poses an increased risk of developing metabolic syndrome and closely associated nonalcoholic fatty liver disease, including liver cancer. Satiety hormone leptin-deficient (ob/ob) mice, considered paradigmatic of nutritional obesity, develop hepatic steatosis but are less prone to developing liver tumors. Sustained activation of peroxisome proliferator-activated receptor α (PPARα) in ob/ob mouse liver increases fatty acid oxidation (FAO), which contributes to attenuation of obesity but enhances liver cancer risk. To further evaluate the role of PPARα-regulated hepatic FAO and energy burning in the progression of fatty liver disease, we generated PPARα-deficient ob/ob (PPARα(Δ)ob/ob) mice. These mice become strikingly more obese compared to ob/ob littermates, with increased white and brown adipose tissue content and severe hepatic steatosis. Hepatic steatosis becomes more severe in fasted PPARα(Δ)ob/ob mice as they fail to up-regulate FAO systems. PPARα(Δ)ob/ob mice also do not respond to peroxisome proliferative and mitogenic effects of PPARα agonist Wy-14,643. Although PPARα(Δ)ob/ob mice are severely obese, there was no significant increase in liver tumor incidence, even when maintained on a diet containing Wy-14,643. W...Continue Reading

References

Jan 1, 1991·Journal of Inherited Metabolic Disease·G van den Berghe
Mar 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J K ReddyN D Lalwani
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·M MaffeiJ M Friedman
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·M ShimabukuroR H Unger
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y T ZhouR H Unger
Feb 14, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B E PetersenG K Michalopoulos
Apr 16, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B E PetersenG K Michalopoulos
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y T ZhouR H Unger
Jun 8, 1999·The Journal of Clinical Investigation·S KerstenW Wahli
Jun 11, 1999·The Journal of Biological Chemistry·M Y WangR H Unger
Feb 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·R FaggioniG Fantuzzi
May 29, 2000·The Journal of Biological Chemistry·M Guerre-MilloB Staels
Nov 14, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·J K Reddy
Aug 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Y LeeR H Unger
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Lelio OrciRoger H Unger
Apr 2, 2004·Nature Medicine·Ronald M EvansYong-Xu Wang
May 26, 2004·Journal of Hepatology·Ira J Fox, Jayanta Roy-Chowdhury
Jul 16, 2005·Endocrinology·M H VickersM Harris
Feb 8, 2006·Biochemical and Biophysical Research Communications·Tao Fu, Jayme Borensztajn
Apr 11, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Janardan K Reddy, M Sambasiva Rao
May 11, 2006·Differentiation; Research in Biological Diversity·Andrea Jochheim-RichterMichael Ott
Jul 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Peter D GluckmanMark A Hanson
Jul 5, 2008·Clinical Reviews in Allergy & Immunology·Frank TackeChristian Trautwein
Jul 11, 2008·American Journal of Physiology. Renal Physiology·Yunfeng ZhouYoufei Guan
Feb 10, 2009·Current Medicinal Chemistry·Tatiana Gurevich-PanigrahiMarek Los
Dec 31, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elisa FabbriniSamuel Klein
Apr 24, 2010·Nuclear Receptor Signaling·Sean R PyperJanardan K Reddy
Apr 12, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang BaiJanardan K Reddy
Jun 28, 2011·Science·Jonathan C CohenHelen H Hobbs
Oct 20, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiansheng HuangJanardan K Reddy
Sep 12, 2012·Annals of Surgery·Vatche G AgopianRonald W Busuttil
Sep 19, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kouichi MiuraEkihiro Seki

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Citations

Sep 4, 2015·The Journal of Physiology·E P S ConceiçãoP C Lisboa
Mar 24, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Kesheng WangYongke Lu
May 3, 2019·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Hassan R Dhaini, Zeina Daher
Mar 11, 2016·Annals of the Rheumatic Diseases·Nadira RuzehajiYannick Allanore
Nov 8, 2018·International Journal of Molecular Sciences·Yi JinZhuqing Ren
Sep 1, 2018·The Journal of Clinical Investigation·Peter R Baker, Jacob E Friedman
Dec 23, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Xiaolin ChenChen Chen
Dec 3, 2016·Current Opinion in Clinical Nutrition and Metabolic Care·Jake P MannValerio Nobili
Jun 25, 2018·Cellular and Molecular Life Sciences : CMLS·David Højland IpsenPernille Tveden-Nyborg
Sep 3, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Xue ChenYongke Lu
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jitendra ShresthaEun-Young Park
Apr 28, 2021·The British Journal of Nutrition·Kely de Paula CorreaJane S Dos R Coimbra
Aug 8, 2021·International Journal of Molecular Sciences·Cheng-Hui WangTzung-Yan Lee
Aug 28, 2021·International Journal of Molecular Sciences·Mounia Tahri-JouteyNorbert Latruffe

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