The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and insulin resistance

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Quanyu ZhangYaling Han

Abstract

Cellular repressor of E1A-stimulated genes (CREG), a novel cellular glycoprotein, has been identified as a suppressor of various cardiovascular diseases because of its capacity to reduce hyperplasia, maintain vascular homeostasis, and promote endothelial restoration. However, the effects and mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown. Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates high-fat diet and leptin deficiency-induced (ob/ob) adverse effects such as obesity, hepatic steatosis, and metabolic disorders, whereas a beneficial effect is conferred by CREG overexpression. Additional experiments demonstrated that c-Jun N-terminal kinase 1 (JNK1) but not JNK2 is largely responsible for the protective effect of CREG on the aforementioned pathologies. Notably, JNK1 inhibition strongly prevents the adverse effects of CREG deletion on steatosis and related metabolic disorders. Mechanistically, CREG interacts directly with apoptosis signal-regulating kinase 1 (ASK1) and inhibits its phosphorylation, thereby blocking the downstream MKK4/7-JNK1 signaling pathway and leading to significantly alleviated obesity, insulin resistance, and hepatic steatosis. Importantly, dramat...Continue Reading

References

Nov 26, 2002·Nature·Jiro HirosumiGökhan S Hotamisligil
May 27, 2004·Diabetes Care·Tara M WallaceDavid R Matthews
Jul 17, 2004·Journal of Hypertension·Li XuLan-Ying Chen
Dec 24, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jörn M SchattenbergMark J Czaja
May 6, 2009·Journal of Cellular and Molecular Medicine·Zhouyan BianHongliang Li
Oct 29, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Ekambaram Padmini, Munuswamy Usha Rani
Sep 14, 2010·Aging·Bengt F BelgardtJens C Brüning
Jun 28, 2011·Journal of Hepatology·Samar H Ibrahim, Gregory J Gores
Jul 5, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kristina M MuellerRichard Moriggl
Dec 17, 2011·Journal of Hepatology·Lars P BechmannAli Canbay
Mar 13, 2012·European Heart Journal·Lokpal S BhatiaChristopher D Byrne
Sep 4, 2012·Journal of Hepatology·Tung-Ming Leung, Natalia Nieto
Jun 12, 2013·Journal of Hepatology·Fabio NascimbeniAmedeo Lonardo
Jul 3, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tao LinRobert Y L Tsai
Jul 23, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Behnam SaberiNeil Kaplowitz
Aug 10, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Andreas L Birkenfeld, Gerald I Shulman
Sep 5, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Matthew J ArmstrongWing-Kin Syn
Apr 29, 2015·Journal of Hepatology·Christopher D Byrne, Giovanni Targher
Apr 29, 2015·Journal of Hepatology·Vlad RatziuArun Sanyal
Jul 15, 2015·Journal of Molecular and Cellular Cardiology·Mingyu SunYaling Han
Dec 15, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giulio MarchesiniRiccardo Dalle Grave
Dec 29, 2015·Gastroenterology·Francisco Javier CuberoChristian Trautwein
Apr 20, 2016·Journal of Hepatology·Sven M FrancqueWilhelmus J Kwanten
May 27, 2016·American Journal of Physiology. Renal Physiology·Greg H TeschDavid J Nikolic-Paterson
Aug 4, 2016·Journal of Hepatology·Raluca PaisFilomena Conti

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Citations

Dec 2, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sanda WinNeil Kaplowitz
Aug 5, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ling YangXiaohua Hou
Feb 1, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lan BaiHongliang Li
Oct 9, 2019·Expert Review of Proteomics·Mohammad Hassan BaigJae-June Dong
Jul 12, 2018·World Journal of Gastroenterology : WJG·Tatsuo KandaMitsuhiko Moriyama
May 10, 2020·Cellular and Molecular Life Sciences : CMLS·Alejandro Gomez-AuliThomas Reinheckel
Nov 13, 2018·Frontiers in Cell and Developmental Biology·Gaby GhobrialLeonard Y Lee
Feb 23, 2019·Expert Review of Gastroenterology & Hepatology·Georgia Kefala, Konstantinos Tziomalos
Mar 21, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lan Bai, Hongliang Li
Nov 21, 2019·The Journal of Dermatological Treatment·Zheng DongZhenyu Chen
Jun 12, 2020·Seminars in Liver Disease·Samar H IbrahimGregory J Gores
Feb 3, 2021·International Journal of Molecular Sciences·Michihiro HashimotoHitoshi Yamashita
Feb 16, 2021·Molecular Metabolism·Beatriz CicuéndezGuadalupe Sabio
Mar 7, 2021·International Journal of Molecular Sciences·Yetirajam Rajesh, Devanand Sarkar
Nov 5, 2021·Journal of Cellular and Molecular Medicine·Yong ZhangQingyan Sun
Oct 15, 2021·Journal of Biochemistry·Tatsuya KusudoHitoshi Yamashita

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