Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice

The Journal of Biological Chemistry
Naoya YahagiNobuhiro Yamada

Abstract

Obesity is a common nutritional problem often associated with diabetes, insulin resistance, and fatty liver (excess fat deposition in liver). Leptin-deficient Lep(ob)/Lep(ob) mice develop obesity and those obesity-related syndromes. Increased lipogenesis in both liver and adipose tissue of these mice has been suggested. We have previously shown that the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) plays a crucial role in the regulation of lipogenesis in vivo. To explore the possible involvement of SREBP-1 in the pathogenesis of obesity and its related syndromes, we generated mice deficient in both leptin and SREBP-1. In doubly mutant Lep(ob/ob) x Srebp-1(-/-) mice, fatty livers were markedly attenuated, but obesity and insulin resistance remained persistent. The mRNA levels of lipogenic enzymes such as fatty acid synthase were proportional to triglyceride accumulation in liver. In contrast, the mRNA abundance of SREBP-1 and lipogenic enzymes in the adipose tissue of Lep(ob)/Lep(ob) mice was profoundly decreased despite sustained fat, which could explain why the SREBP-1 disruption had little effect on obesity. In conclusion, SREBP-1 regulation of lipogenesis is highly involved in the development of ...Continue Reading

References

Jan 1, 1977·Metabolism: Clinical and Experimental·L Herberg, D L Coleman
Mar 1, 1996·Lipids·M T ClandininC J Field
Nov 1, 1996·Cell·B M Spiegelman, J S Flier
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·P H WeinstockJ L Breslow
Feb 14, 1998·The Journal of Clinical Investigation·J B KimB M Spiegelman
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J D HortonH Shimano
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·M ForetzF Foufelle
Nov 24, 1999·The American Journal of Medicine·G MarchesiniN Melchionda
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·I ShimomuraJ L Goldstein
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·J S Flier, A N Hollenberg
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·J OsugaN Yamada
Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·S T NadlerA D Attie
Dec 1, 1950·The Journal of Heredity·A M INGALLSG D SNELL
Jun 29, 1951·Science·J MAYERM M DICKIE

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Citations

Feb 7, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hitoshi Shimano
Oct 3, 2008·In Vitro Cellular & Developmental Biology. Animal·Motoyuki KohjimaMakoto Nakamuta
May 5, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Naoya YahagiNobuhiro Yamada
Dec 31, 2004·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Michael Charlton
Dec 5, 2013·Nature Communications·Takahiro HorieKoh Ono
Jun 4, 2004·The New England Journal of Medicine·Kevin R ShortCraig S Stump
Feb 11, 2010·The Journal of Biological Chemistry·Ana Fernández-AlvarezMarta Casado
Oct 28, 2009·Journal of Medicinal Food·Chan Hum ParkTakako Yokozawa
May 8, 2009·Current Opinion in Lipidology·Joel T Haas, Sudha B Biddinger
May 14, 2010·Current Opinion in Lipidology·Mélissa FlammentFabienne Foufelle
Apr 13, 2007·Annual Review of Nutrition·Catherine PosticJean Girard
Feb 8, 2006·Annual Review of Physiology·Sudha B Biddinger, C Ronald Kahn
Feb 18, 2010·American Journal of Physiology. Endocrinology and Metabolism·Min LuJerrold M Olefsky
Oct 30, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Haiyan ZhangSalman Azhar
May 18, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·Guo Guang WangCui Zhang
Jul 21, 2011·Journal of Lipids·Klementina Fon Tacer, Damjana Rozman
Sep 14, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·Takako YokozawaJi Hyun Kim
Mar 6, 2003·The Journal of Clinical Investigation·Kimihiko MatsusueFrank J Gonzalez
Apr 16, 2004·The Journal of Clinical Investigation·Alan D Attie
Jul 16, 2004·The Journal of Clinical Investigation·Jeffrey D Browning, Jay D Horton
Feb 25, 2010·Journal of Lipid Research·Takashi YamamotoHitoshi Shimano
Nov 11, 2008·Journal of Lipid Research·Cynthia A NagleRosalind A Coleman
Oct 13, 2009·Endocrinology·Michael K BadmanEleftheria Maratos-Flier
Feb 1, 2008·Molecular Medicine·Herbert Tilg, Alexander R Moschen
Jan 24, 2013·Journal of Clinical Biochemistry and Nutrition·Chie MutoChikako Kiyose
Jun 3, 2011·World Journal of Gastroenterology : WJG·Jian-Hong ChuZhi-Ling Yu
Jun 3, 2011·World Journal of Gastroenterology : WJG·Yang-Gun Suh, Won-Il Jeong

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