27-Hydroxycholesterol Inhibits Sterol Regulatory Element-Binding Protein 1 Activation and Hepatic Lipid Accumulation in Mice

Obesity
Di LiMin Xia

Abstract

Although 27-hydroxycholesterol (27-HC) has been reported as a potent regulator of lipid homeostasis, its role in hepatic lipogenesis remains obscure. The present study was designed to investigate the impact of 27-HC on sterol regulatory element-binding protein 1 (SREBP-1) and hepatic steatosis. In this study, the 27-HC level in mice was upregulated by overexpressing CYP27A1 or treating primary hepatocytes with 27-HC, and then the hepatic lipid accumulation was detected. 27-HC inhibited hepatic lipid accumulation and decreased the levels of the mature active form of SREBP-1. The expression of lipogenic genes, including acetyl coenzyme A carboxylase, fatty acid synthase, stearoyl-coenzyme A desaturase-1, and glycerol-3-phosphate acyltransferase, were also suppressed after 27-HC intervention. Furthermore, 27-HC induced expression of insulin-induced gene-2 (Insig-2), an endoplasmic reticulum protein that prevents SREBP activation, both in vivo and in vitro. The inhibitory effect of 27-HC on SREBP-1 activation was absent when Insig-2 was silenced. Finally, coimmunoprecipitation showed that 27-HC promoted the binding of Insig-2 to SREBP-1. These studies demonstrated the suppressive effect of 27-HC on hepatic lipid accumulation and re...Continue Reading

References

Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·F E ThorngateM B Elam
Jan 27, 1999·Atherosclerosis·A J Brown, W Jessup
Jun 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·J K KimG I Shulman
Aug 16, 2001·The Journal of Biological Chemistry·X FuE G Lund
Nov 8, 2001·Free Radical Research·S Garcia-CrusetM J Mitchinson
Sep 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Daisuke YabeJoseph L Goldstein
Mar 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Daisuke YabeMichael S Brown
Nov 27, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jeffrey D BrowningHelen H Hobbs
Apr 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Arun RadhakrishnanJoseph L Goldstein
Sep 18, 2007·Nature Medicine·Michihisa UmetaniDavid J Mangelsdorf
Feb 23, 2008·Trends in Endocrinology and Metabolism : TEM·Rajendra RaghowMarshall B Elam
Jul 16, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiaomei QinNanping Wang
Nov 19, 2008·Journal of Hepatology·Jian-Gao Fan, Geoffrey C Farrell
Mar 1, 2011·Trends in Endocrinology and Metabolism : TEM·Michihisa Umetani, Philip W Shaul
Apr 21, 2011·Cold Spring Harbor Perspectives in Biology·Jin Ye, Russell A DeBose-Boyd
Jul 17, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Janet D SparksKhosrow Adeli
Oct 9, 2012·Gastroenterology·Veerle BieghsRonit Shiri-Sverdlov
Nov 28, 2013·The Journal of Biological Chemistry·Jiehan LiVassilios Papadopoulos
Jun 6, 2014·Nature·Rachel J PerryGerald I Shulman
Jan 5, 2016·The Journal of Clinical Investigation·Varman T Samuel, Gerald I Shulman
Aug 30, 2016·Cell Metabolism·Manuel Roqueta-RiveraTimothy F Osborne

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Citations

Feb 28, 2019·Nature Reviews. Immunology·Katie L O'Brien, David K Finlay
Aug 6, 2019·Frontiers in Endocrinology·Urša KovačTadeja Režen
Oct 17, 2019·Frontiers in Immunology·Iñigo TerrénFrancisco Borrego
Jul 8, 2020·Nature Reviews. Cancer·Robert D Leone, Jonathan D Powell
Feb 11, 2020·Frontiers in Immunology·Ombretta MelaiuDoriana Fruci
Mar 7, 2021·Cancers·Ronan Talty, Kelly Olino

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