{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:16:04Z","timestamp":1790957764463,"version":"4.1.0"},"reference-count":150,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T00:00:00Z","timestamp":1684540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Virginia Commonwealth University Internal Medicine Pilot Project","award":["411864"],"award-info":[{"award-number":["411864"]}]},{"name":"Virginia Commonwealth University Internal Medicine Pilot Project","award":["I01 BX000197-07"],"award-info":[{"award-number":["I01 BX000197-07"]}]},{"name":"U.S. Department of Veterans Affairs","award":["411864"],"award-info":[{"award-number":["411864"]}]},{"name":"U.S. Department of Veterans Affairs","award":["I01 BX000197-07"],"award-info":[{"award-number":["I01 BX000197-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The rising prevalence of nonalcoholic fatty liver disease (NAFLD)-related cirrhosis highlights the need for a better understanding of the molecular mechanisms responsible for driving the transition of hepatic steatosis (fatty liver; NAFL) to steatohepatitis (NASH) and fibrosis\/cirrhosis. Obesity-related insulin resistance (IR) is a well-known hallmark of early NAFLD progression, yet the mechanism linking aberrant insulin signaling to hepatocyte inflammation has remained unclear. Recently, as a function of more distinctly defining the regulation of mechanistic pathways, hepatocyte toxicity as mediated by hepatic free cholesterol and its metabolites has emerged as fundamental to the subsequent necroinflammation\/fibrosis characteristics of NASH. More specifically, aberrant hepatocyte insulin signaling, as found with IR, leads to dysregulation in bile acid biosynthetic pathways with the subsequent intracellular accumulation of mitochondrial CYP27A1-derived cholesterol metabolites, (25R)26-hydroxycholesterol and 3\u03b2-Hydroxy-5-cholesten-(25R)26-oic acid, which appear to be responsible for driving hepatocyte toxicity. These findings bring forth a \u201ctwo-hit\u201d interpretation as to how NAFL progresses to NAFLD: abnormal hepatocyte insulin signaling, as occurs with IR, develops as a \u201cfirst hit\u201d that sequentially drives the accumulation of toxic CYP27A1-driven cholesterol metabolites as the \u201csecond hit\u201d. In the following review, we examine the mechanistic pathway by which mitochondria-derived cholesterol metabolites drive the development of NASH. Insights into mechanistic approaches for effective NASH intervention are provided.<\/jats:p>","DOI":"10.3390\/cells12101434","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T01:31:46Z","timestamp":1684719106000},"page":"1434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mitochondrial Cholesterol Metabolites in a Bile Acid Synthetic Pathway Drive Nonalcoholic Fatty Liver Disease: A Revised \u201cTwo-Hit\u201d Hypothesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-6903","authenticated-orcid":false,"given":"Genta","family":"Kakiyama","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA"},{"name":"Research Services, Central Virginia Veterans Affairs Healthcare System, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rodriguez-Agudo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA"},{"name":"Research Services, Central Virginia Veterans Affairs Healthcare System, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Pandak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA"},{"name":"Research Services, Central Virginia Veterans Affairs Healthcare System, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"key":"ref_1","first-page":"434","article-title":"Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease","volume":"55","author":"Ludwig","year":"1980","journal-title":"Mayo Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0140-6736(15)00803-X","article-title":"Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study","volume":"387","author":"Armstrong","year":"2016","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0140-6736(18)31773-2","article-title":"Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: A randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial","volume":"392","author":"Birkenfeld","year":"2018","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/oby.22794","article-title":"Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5","volume":"28","author":"Kushner","year":"2020","journal-title":"Obesity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4093\/dmj.2019.0043","article-title":"Understanding Bile Acid Signaling in Diabetes: From Pathophysiology to Therapeutic Targets","volume":"43","author":"Ferrell","year":"2019","journal-title":"Diabetes Metab. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.livres.2019.05.001","article-title":"The acidic pathway of bile acid synthesis: Not just an alternative pathway","volume":"3","author":"Pandak","year":"2019","journal-title":"Liver Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s13238-020-00804-9","article-title":"Targeting the alternative bile acid synthetic pathway for metabolic diseases","volume":"12","author":"Jia","year":"2021","journal-title":"Protein Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/hep4.1801","article-title":"Role of Cholesterol-Associated Steatohepatitis in the Development of NASH","volume":"6","author":"Horn","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jsbmb.2019.01.011","article-title":"Mitochondrial oxysterol biosynthetic pathway gives evidence for CYP7B1 as controller of regulatory oxysterols","volume":"189","author":"Kakiyama","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1006\/bbrc.2001.2013","article-title":"Cholesterol, Hydroxycholesterols, and Bile Acids","volume":"292","author":"Javitt","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100165","DOI":"10.1016\/j.jlr.2021.100165","article-title":"Cholesterol metabolism: From lipidomics to immunology","volume":"63","author":"Griffiths","year":"2022","journal-title":"J. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1194\/jlr.RA120000924","article-title":"Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: A pathway for NAFL to NASH transition","volume":"61","author":"Kakiyama","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"G488","DOI":"10.1152\/ajpgi.00179.2022","article-title":"Coffee modulates insulin-HNF-4alpha-Cyp7b1 pathway and reduces oxysterol driven liver toxicity in a NAFLD mouse model","volume":"323","author":"Kakiyama","year":"2022","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100363","DOI":"10.1016\/j.jlr.2023.100363","article-title":"Insulin dysregulation drives mitochondrial cholesterol metabolite accumulation: Initiating hepatic toxicity in NAFLD","volume":"64","author":"Minowa","year":"2023","journal-title":"J. Lipid Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/hep.30429","article-title":"Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease","volume":"70","author":"Khan","year":"2019","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1210\/er.2019-00034","article-title":"The Liver as an Endocrine Organ\u2014Linking NAFLD and Insulin Resistance","volume":"40","author":"Watt","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30729","DOI":"10.1074\/jbc.273.46.30729","article-title":"Oxysterol Regulation of Steroidogenic Acute Regulatory Protein Gene Expression","volume":"273","author":"Christenson","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1749-6632.1993.tb38722.x","article-title":"The Interaction of Dietary Cholesterol and Specific Fatty Acids in the Regulation of LDL Receptor Activity and Plasma LDL-Cholesterol Concentrations","volume":"676","author":"Dietschy","year":"1993","journal-title":"Ann. New York Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1194\/jlr.RA119000395","article-title":"Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition","volume":"61","author":"Honda","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.bbadis.2018.05.011","article-title":"Animal models to study bile acid metabolism","volume":"1865","author":"Li","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_29","first-page":"90","article-title":"Mitochondrial cholesterol import","volume":"1862","author":"Elustondo","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"48158","DOI":"10.1074\/jbc.M205244200","article-title":"Transport of Cholesterol into Mitochondria Is Rate-limiting for Bile Acid Synthesis via the Alternative Pathway in Primary Rat Hepatocytes","volume":"277","author":"Pandak","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1002\/hep.1840400421","article-title":"Overexpression of cholesterol transporter StAR increasesin vivo rates of bile acid synthesis in the rat and mouse","volume":"40","author":"Ren","year":"2004","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11540","DOI":"10.1073\/pnas.94.21.11540","article-title":"Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia","volume":"94","author":"Caron","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1194\/jlr.M400233-JLR200","article-title":"Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis","volume":"45","author":"Ren","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.redox.2017.02.024","article-title":"MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content","volume":"12","author":"Balboa","year":"2017","journal-title":"Redox Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.steroids.2012.02.006","article-title":"27-Hydroxycholesterol, does it exist? On the nomenclature and stereochemistry of 26-hydroxylated sterols","volume":"77","author":"Fakheri","year":"2012","journal-title":"Steroids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0022-2275(20)38509-6","article-title":"Occurrence of 3 beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha-dihydroxy-5-cholestenoic acid, and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid as normal constituents in human blood","volume":"29","author":"Axelson","year":"1988","journal-title":"J. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1016\/S0022-2275(20)38199-2","article-title":"Concentrations of cholestenoic acids in plasma from patients with liver disease","volume":"30","author":"Axelson","year":"1989","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/S0022-2275(20)38200-6","article-title":"Concentrations of cholestenoic acids in plasma from patients with reduced intestinal reabsorption of bile acids","volume":"30","author":"Axelson","year":"1989","journal-title":"J. Lipid Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/cvr\/cvq015","article-title":"Overexpression of steroidogenic acute regulatory protein increases macrophage cholesterol efflux to apolipoprotein AI","volume":"86","author":"Taylor","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1210\/endo.141.11.7772","article-title":"Cholestenoic Acid Is a Naturally Occurring Ligand for Liver X Receptor \u03b1**This work was supported by NIH grants","volume":"141","author":"Song","year":"2000","journal-title":"Endocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"38378","DOI":"10.1074\/jbc.M105805200","article-title":"27-Hydroxycholesterol Is an Endogenous Ligand for Liver X Receptor in Cholesterol-loaded Cells","volume":"276","author":"Fu","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102733","DOI":"10.1016\/j.jbc.2022.102733","article-title":"Hydroxylation site\u2013specific and production-dependent effects of endogenous oxysterols on cholesterol homeostasis: Implications for SREBP-2 and LXR","volume":"299","author":"Saito","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jsbmb.2016.02.001","article-title":"On the regulatory importance of 27-hydroxycholesterol in mouse liver","volume":"169","author":"Heverin","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0022-2275(20)38127-X","article-title":"Cerebrotendinous xanthomatosis: Reduced serum 26-hydroxycholesterol","volume":"23","author":"Javitt","year":"1982","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbrc.2010.02.140","article-title":"Cerebrotendinous xanthomatosis: An inborn error in bile acid synthesis with defined mutations but still a challenge","volume":"396","author":"Hansson","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s12519-018-0151-9","article-title":"Liver transplantation due to cerebrotendinous xanthomatosis end-stage liver disease","volume":"14","author":"Shen","year":"2018","journal-title":"World J. Pediatr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e14318","DOI":"10.1111\/petr.14318","article-title":"Liver transplantation in an infant with cerebrotendinous xanthomatosis, cholestasis, and rapid evolution of liver failure","volume":"26","author":"Pietrobattista","year":"2022","journal-title":"Pediatr. Transplant."},{"key":"ref_48","first-page":"616582","article-title":"Sterol 27-Hydroxylase Deficiency as a Cause of Neonatal Cholestasis: Report of 2 Cases and Review of the Literature","volume":"8","author":"Ciara","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_49","first-page":"561","article-title":"Severe Neonatal Cholestasis in Cerebrotendinous Xanthomatosis: Genetics, Immunostaining, Mass Spectrometry","volume":"65","author":"Gong","year":"2017","journal-title":"J. Craniofacial Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1055\/s-2007-985073","article-title":"Inborn Errors of Bile Acid Metabolism","volume":"27","author":"Heubi","year":"2007","journal-title":"Semin. Liver Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jacl.2018.06.008","article-title":"Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis","volume":"12","author":"Duell","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0022-2275(20)32094-0","article-title":"Structure and functions of human oxysterol 7\u03b1-hydroxylase cDNAs and gene CYP7B1","volume":"40","author":"Wu","year":"1999","journal-title":"J. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"28485","DOI":"10.1074\/jbc.R109.042168","article-title":"CYP7B1: One Cytochrome P450, Two Human Genetic Diseases, and Multiple Physiological Functions","volume":"284","author":"Stiles","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1016\/S0021-9258(19)84923-2","article-title":"Cholic Acid Synthesis from 26-Hydroxycholesterol and 3-Hydroxy-5-cholestenoic Acid in the Rabbit","volume":"264","author":"Ayaki","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1172\/JCI2962","article-title":"Identification of a new inborn error in bile acid synthesis: Mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease","volume":"102","author":"Setchell","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s10545-014-9695-6","article-title":"Liver disease in infancy caused by oxysterol 7\u03b1-hydroxylase deficiency: Successful treatment with chenodeoxycholic acid","volume":"37","author":"Dai","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/lt.22331","article-title":"Successful heterozygous living donor liver transplantation for an oxysterol 7\u03b1-hydroxylase deficiency in a Japanese patient","volume":"17","author":"Mizuochi","year":"2011","journal-title":"Liver Transplant."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1046\/j.1442-200x.2000.01292.x","article-title":"3beta-Hydroxy-Delta5-C27-steroid dehydrogenase\/isomerase deficiency in a 23-year-old woman","volume":"42","author":"Kobayashi","year":"2000","journal-title":"Pediatr. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1007\/s10620-020-06722-4","article-title":"Bile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment","volume":"66","author":"Kimura","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16536","DOI":"10.1074\/jbc.M001811200","article-title":"Disruption of the Oxysterol 7\u03b1-Hydroxylase Gene in Mice","volume":"275","author":"Lund","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_61","unstructured":"Minowa, K., Rodriguez-Agudo, D., Suzuki, M., Hirai, S., Muto, Y., Su, L., Mitamura, K., Ikegawa, S., Heuman, D.M., and Zhou, H. (2022). Hepatology, WILEY."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/path.5477","article-title":"Sex-opposed inflammatory effects of 27-hydroxycholesterol are mediated via differences in estrogen signaling","volume":"251","author":"Houben","year":"2020","journal-title":"J. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1002\/hep.30333","article-title":"Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis","volume":"69","author":"Farrell","year":"2018","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1194\/jlr.M093229","article-title":"Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis","volume":"60","author":"Raselli","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4062\/biomolther.2018.175","article-title":"Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice","volume":"27","author":"Na","year":"2019","journal-title":"Biomol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Evangelakos, I., Schwinge, D., Worthmann, A., John, C., Roeder, N., Pertzborn, P., Behrens, J., Schramm, C., Scheja, L., and Heeren, J. (2021). Oxysterol 7-\u03b1 Hydroxylase (CYP7B1) Attenuates Metabolic-Associated Fatty Liver Disease in Mice at Thermoneutrality. Cells, 10.","DOI":"10.3390\/cells10102656"},{"key":"ref_67","first-page":"159135","article-title":"Identification cholesterol metabolites altered before the onset of nonalcoholic steatohepatitis by targeted metabolomics","volume":"1867","author":"Shoji","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"114664","DOI":"10.1016\/j.taap.2019.114664","article-title":"Altered bile acid composition and disposition in a mouse model of non-alcoholic steatohepatitis","volume":"379","author":"Suga","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0378-1119(01)00541-8","article-title":"Transcriptional regulation of human oxysterol 7\u03b1-hydroxylase gene (CYP7B1) by Sp1","volume":"272","author":"Wu","year":"2001","journal-title":"Gene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1194\/jlr.M500430-JLR200","article-title":"Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4\u03b1","volume":"47","author":"Inoue","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.molmed.2004.09.004","article-title":"HNF-4\u03b1: From MODY to late-onset type 2 diabetes","volume":"10","author":"Gupta","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_72","first-page":"442","article-title":"Effect of Hyperinsulinemia and Type 2 Diabetes-Like Hyperglycemia on Expression of Hepatic Cytochrome P450 and GlutathioneS-Transferase Isoforms in a New Zealand Obese-Derived Mouse Backcross Population","volume":"302","author":"Pass","year":"2002","journal-title":"Experiment"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1507\/endocrj.EJ12-0258","article-title":"Analysis of hepatic gene expression profile in a spontaneous mouse model of type 2 diabetes under a high sucrose diet","volume":"60","author":"Nojima","year":"2013","journal-title":"Endocr. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nm1785","article-title":"Hepatic insulin resistance directly promotes formation of cholesterol gallstones","volume":"14","author":"Biddinger","year":"2008","journal-title":"Nat. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jsbmb.2008.08.004","article-title":"Involvement of the PI3K\/Akt pathway in estrogen-mediated regulation of human CYP7B1: Identification of CYP7B1 as a novel target for PI3K\/Akt and MAPK signalling","volume":"112","author":"Tang","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e00654-17","DOI":"10.1128\/MCB.00654-17","article-title":"Regulation of Cholesterol Sulfotransferase SULT2B1b by Hepatocyte Nuclear Factor 4\u03b1 Constitutes a Negative Feedback Control of Hepatic Gluconeogenesis","volume":"38","author":"Bi","year":"2018","journal-title":"Mol. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1053\/jhep.2003.50351","article-title":"Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion","volume":"38","author":"Coll","year":"2003","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: Where they are and how they behave","volume":"9","author":"Voelker","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jhep.2008.12.016","article-title":"Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH","volume":"50","author":"Caballero","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0378-1119(03)00631-0","article-title":"Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4\u03b1 (HNF4\u03b1)","volume":"313","author":"Chen","year":"2003","journal-title":"Gene"},{"key":"ref_81","first-page":"111","article-title":"Detection of the steroidogenic acute regulatory protein, StAR, in human liver cells","volume":"1733","author":"Hall","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/j.jhep.2021.01.028","article-title":"STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway","volume":"74","author":"Vallejo","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cmet.2006.07.006","article-title":"Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis","volume":"4","author":"Caballero","year":"2006","journal-title":"Cell Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.3748\/wjg.v13.i22.3071","article-title":"Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse","volume":"13","author":"Tichauer","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"33928","DOI":"10.1074\/jbc.M210943200","article-title":"Cholesterol Impairs the Adenine Nucleotide Translocator-mediated Mitochondrial Permeability Transition through Altered Membrane Fluidity","volume":"278","author":"Colell","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_86","first-page":"G456","article-title":"Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice","volume":"289","author":"Wu","year":"2005","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1042\/bj2890703","article-title":"Cholesterol increase in mitochondria: Its effect on inner-membrane functions, submitochondrial localization and ultrastructural morphology","volume":"289","author":"Echegoyen","year":"1993","journal-title":"Biochem. J."},{"key":"ref_88","first-page":"117","article-title":"Mitochondrial cholesterol in health and disease","volume":"24","author":"Mari","year":"2009","journal-title":"Histol Histopathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1128\/MCB.00494-12","article-title":"Cellular Adaptation to Anthrax Lethal Toxin-Induced Mitochondrial Cholesterol Enrichment, Hyperpolarization, and Reactive Oxygen Species Generation through Downregulating MLN64 in Macrophages","volume":"32","author":"Ha","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1089\/ars.2009.2695","article-title":"Mitochondrial Glutathione, a Key Survival Antioxidant","volume":"11","author":"Morales","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101214","DOI":"10.1016\/j.redox.2019.101214","article-title":"Cholesterol enrichment in liver mitochondria impairs oxidative phosphorylation and disrupts the assembly of respiratory supercomplexes","volume":"24","author":"Fucho","year":"2019","journal-title":"Redox Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/2211-5463.12123","article-title":"Hepatic caveolin-1 is enhanced in Cyp27a1\/ApoE double knockout mice","volume":"6","author":"Zurkinden","year":"2016","journal-title":"FEBS Open Bio"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"BSR20171162","DOI":"10.1042\/BSR20171162","article-title":"Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice","volume":"38","author":"Zurkinden","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Zhao, M., Xing, Y., Liu, L., Fan, X., Liu, L., Geng, T., and Gong, D. (2020). GC-TOF-MS-Based Metabolomics Analyses of Liver and Intestinal Contents in the Overfed vs. Normally-Fed Geese. Animals, 10.","DOI":"10.3390\/ani10122375"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.plipres.2012.11.002","article-title":"Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis","volume":"52","author":"Musso","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"881","DOI":"10.3109\/10715762.2013.835048","article-title":"Oxysterols and redox signaling in the pathogenesis of non-alcoholic fatty liver disease","volume":"47","author":"Serviddio","year":"2013","journal-title":"Free. Radic. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.redox.2017.11.016","article-title":"Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression","volume":"15","author":"Bellanti","year":"2017","journal-title":"Redox Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1016\/j.freeradbiomed.2014.10.594","article-title":"Oxysterols induce mitochondrial impairment and hepatocellular toxicity in non-alcoholic fatty liver disease","volume":"75","author":"Bellanti","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"116464","DOI":"10.1016\/j.lfs.2019.05.020","article-title":"Mitochondrial DNA in liver inflammation and oxidative stress","volume":"236","author":"Zhang","year":"2019","journal-title":"Life Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1172\/JCI121842","article-title":"STING-mediated inflammation in Kupffer cells contributes to progression of nonalcoholic steatohepatitis","volume":"129","author":"Yu","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.cmet.2014.05.013","article-title":"The Cholesterol Metabolite 27-Hydroxycholesterol Promotes Atherosclerosis via Proinflammatory Processes Mediated by Estrogen Receptor Alpha","volume":"20","author":"Umetani","year":"2014","journal-title":"Cell Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/hep.32562","article-title":"Endoplasmic reticulum stress in liver diseases","volume":"77","author":"Ajoolabady","year":"2023","journal-title":"Hepatology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jhep.2018.06.008","article-title":"Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease","volume":"69","author":"Lebeaupin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/ars.2010.3790","article-title":"Endoplasmic Reticulum Stress and the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease","volume":"15","author":"Gentile","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature09968","article-title":"Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity","volume":"473","author":"Fu","year":"2011","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"19320","DOI":"10.1073\/pnas.1012044107","article-title":"Sarco(endo)plasmic reticulum Ca2+ -ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity","volume":"107","author":"Park","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cmet.2020.03.010","article-title":"Cholesterol Stabilizes TAZ in Hepatocytes to Promote Experimental Non-alcoholic Steatohepatitis","volume":"31","author":"Wang","year":"2020","journal-title":"Cell Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.cmet.2016.09.016","article-title":"Hepatocyte TAZ\/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis","volume":"24","author":"Wang","year":"2016","journal-title":"Cell Metab."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1194\/jlr.M400501-JLR200","article-title":"Human StarD5, a cytosolic StAR-related lipid binding protein","volume":"46","author":"Ren","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1194\/jlr.M500447-JLR200","article-title":"Localization of StarD5 cholesterol binding protein","volume":"47","author":"Ren","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1194\/jlr.M091967","article-title":"StarD5: An ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis","volume":"60","author":"Malacrida","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_112","unstructured":"Rodriguez-Agudo, D., Kakiyama, G., and Pandak Jr, W.M. (2022). Hepatology, Willey."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jhep.2022.09.020","article-title":"Mitochondrial alterations in fatty liver diseases","volume":"78","author":"Fromenty","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.metabol.2011.11.014","article-title":"Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor\/sterol regulatory element binding protein\u20131c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease","volume":"61","author":"Bai","year":"2012","journal-title":"Metabolism"},{"key":"ref_115","first-page":"G87","article-title":"Inhibition of LXR signaling by SULT2B1b promotes liver regeneration after partial hepatectomy in mouse models of nonalcoholic fatty liver disease","volume":"319","author":"Zhang","year":"2020","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1124\/mol.112.081505","article-title":"5-Cholesten-3\u03b2,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model","volume":"83","author":"Xu","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tai, Y.-L., Zhao, D., Zhang, Y., Yan, J., Kakiyama, G., Wang, X., Gurley, E.C., Liu, J., and Liu, J. (2021). Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways. Cells, 10.","DOI":"10.3390\/cells10020210"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"8829","DOI":"10.1039\/D2FO01161A","article-title":"The different effects of psyllium husk and orlistat on weight control, the amelioration of hypercholesterolemia and non-alcohol fatty liver disease in obese mice induced by a high-fat diet","volume":"13","author":"Deng","year":"2022","journal-title":"Food Funct."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"771976","DOI":"10.3389\/fphar.2021.771976","article-title":"Ilexsaponin A1 Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism in Mice","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1053\/j.gastro.2019.04.023","article-title":"Endoplasmic Reticulum Stress-Induced Upregulation of STARD1 Promotes Acetaminophen-Induced Acute Liver Failure","volume":"157","author":"Torres","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"102052","DOI":"10.1016\/j.redox.2021.102052","article-title":"Acid ceramidase improves mitochondrial function and oxidative stress in Niemann-Pick type C disease by repressing STARD1 expression and mitochondrial cholesterol accumulation","volume":"45","author":"Torres","year":"2021","journal-title":"Redox Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jhep.2013.05.023","article-title":"ASMase is required for chronic alcohol induced hepatic endoplasmic reticulum stress and mitochondrial cholesterol loading","volume":"59","author":"Fernandez","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1016\/j.bmcl.2012.04.058","article-title":"Identification of small-molecule inhibitors of the steroidogenic acute regulatory protein (STARD1) by structure-based design","volume":"22","author":"Akula","year":"2012","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_124","first-page":"258","article-title":"Phenotypic variations in lipoid congenital adrenal hyperplasia","volume":"3","author":"Bhangoo","year":"2006","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1210\/jc.2006-1565","article-title":"Nonclassic Congenital Lipoid Adrenal Hyperplasia: A New Disorder of the Steroidogenic Acute Regulatory Protein with Very Late Presentation and Normal Male Genitalia","volume":"91","author":"Baker","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1210\/jc.2009-0467","article-title":"Nonclassic Lipoid Congenital Adrenal Hyperplasia Masquerading as Familial Glucocorticoid Deficiency","volume":"94","author":"Metherell","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3389\/fnins.2016.00527","article-title":"Thirty-Eight-Year Follow-Up of Two Sibling Lipoid Congenital Adrenal Hyperplasia Patients Due to Homozygous Steroidogenic Acute Regulatory (STARD1) Protein Mutation. Molecular Structure and Modeling of the STARD1 L275P Mutation","volume":"10","author":"Khoury","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s10549-017-4562-4","article-title":"Vitamin D supplementation decreases serum 27-hydroxycholesterol in a pilot breast cancer trial","volume":"167","author":"Going","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1124\/mol.115.099598","article-title":"Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy","volume":"88","author":"Mast","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1167\/iovs.10-6021","article-title":"Cholestenoic Acid Is an Important Elimination Product of Cholesterol in the Retina: Comparison of Retinal Cholesterol Metabolism with That in the Brain","volume":"52","author":"Mast","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Tang, Y.-P., Gong, J.-Y., Setchell, K.D.R., Zhang, W., Zhao, J., and Wang, J.-S. (2021). Successful treatment of infantile oxysterol 7\u03b1-hydroxylase deficiency with oral chenodeoxycholic acid. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-01749-x"},{"key":"ref_132","first-page":"283","article-title":"Cerebrotendinous xanthomatosis","volume":"24","year":"2013","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1124\/mol.117.110742","article-title":"Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo","volume":"93","author":"Lam","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.atherosclerosis.2010.11.021","article-title":"Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR\/SREBP-1c signaling pathway in human aortic endothelial cells","volume":"214","author":"Bai","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Wang, Y., Li, X., and Ren, S. (2020). Cholesterol Metabolites 25-Hydroxycholesterol and 25-Hydroxycholesterol 3-Sulfate Are Potent Paired Regulators: From Discovery to Clinical Usage. Metabolites, 11.","DOI":"10.3390\/metabo11010009"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"100063","DOI":"10.1016\/j.jlr.2021.100063","article-title":"25-Hydroxycholesterol 3-sulfate is an endogenous ligand of DNA methyltransferases in hepatocytes","volume":"62","author":"Wang","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Wang, Y., Pandak, W.M., Lesnefsky, E.J., Hylemon, P.B., and Ren, S. (2021). 25-Hydroxycholesterol 3-Sulfate Recovers Acetaminophen Induced Acute Liver Injury via Stabilizing Mitochondria in Mouse Models. Cells, 10.","DOI":"10.3390\/cells10113027"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Fu, S., Fan, J., Blanco, J., Gim\u00e9nez-Cassina, A., Danial, N.N., Watkins, S.M., and Hotamisligil, G.S. (2012). Polysome Profiling in Liver Identifies Dynamic Regulation of Endoplasmic Reticulum Translatome by Obesity and Fasting. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002902"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1210\/en.2017-00288","article-title":"Attenuated Effects of Bile Acids on Glucose Metabolism and Insulin Sensitivity in a Male Mouse Model of Prenatal Undernutrition","volume":"158","author":"Ma","year":"2017","journal-title":"Endocrinology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"701003","DOI":"10.3389\/fphar.2021.701003","article-title":"Astragalus Polysaccharides Ameliorate Diet-Induced Gallstone Formation by Modulating Synthesis of Bile Acids and the Gut Microbiota","volume":"12","author":"Zhuang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.apsb.2019.02.004","article-title":"Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters","volume":"9","author":"Sun","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"8134918","DOI":"10.1155\/2018\/8134918","article-title":"Protective Effects of Yinchenhao Decoction on Cholesterol Gallstone in Mice Fed a Lithogenic Diet by Regulating LXR, CYP7A1, CYP7B1, and HMGCR Pathways","volume":"2018","author":"Meng","year":"2018","journal-title":"Evid. Based Complement Altern. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"111819","DOI":"10.1016\/j.foodres.2022.111819","article-title":"Comparative multiomics study of the effects of Ellagic acid on the gut environment in young and adult mice","volume":"161","author":"Duan","year":"2022","journal-title":"Food Res. Int."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1111\/liv.15025","article-title":"Zonation in NASH\u2014A key paradigm for understanding pathophysiology and clinical outcomes","volume":"41","author":"Steinman","year":"2021","journal-title":"Liver Int."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1016\/j.apsb.2021.05.023","article-title":"Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1","volume":"11","author":"Rizzolo","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s00125-013-3149-9","article-title":"The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: A randomised controlled trial","volume":"57","author":"Takeshita","year":"2014","journal-title":"Diabetologia"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Cho, Y., Rhee, H., Kim, Y.-E., Lee, M., Lee, B.-W., Kang, E.S., Cha, B.-S., Choi, J.-Y., and Lee, Y.-H. (2022). Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: An open-label randomized controlled trial (ESSENTIAL study). BMC Med., 20.","DOI":"10.1186\/s12916-022-02288-2"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0005-2760(96)00152-X","article-title":"Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques","volume":"1344","author":"Crisby","year":"1997","journal-title":"Biochim. Biophys. Acta (BBA) Lipids Lipid Metab."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1042\/CS20120358","article-title":"Mitochondrial (dys)function and regulation of macrophage cholesterol efflux","volume":"124","author":"Allen","year":"2013","journal-title":"Clin. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1194\/jlr.R049437","article-title":"Key discoveries in bile acid chemistry and biology and their clinical applications: History of the last eight decades","volume":"55","author":"Hofmann","year":"2014","journal-title":"J. Lipid Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/10\/1434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:39:11Z","timestamp":1760125151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/10\/1434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,20]]},"references-count":150,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cells12101434"],"URL":"https:\/\/doi.org\/10.3390\/cells12101434","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,20]]}}}