{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:08:20Z","timestamp":1788469700089,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) with or without atorvastatin to induce NASH and hepatic fibrosis. Besides the well-known plasma cholesterol lowering (\u221230%) and anti-atherogenic effects (severe lesion size \u221248%), atorvastatin significantly reduced hepatic steatosis (\u221222%), the number of aggregated inflammatory cells in the liver (\u221280%) and hepatic fibrosis (\u221292%) compared to WTD-fed mice. Furthermore, atorvastatin-treated mice showed less immunohistochemically stained areas of inflammation markers. Atorvastatin prevented accumulation of free cholesterol in the form of cholesterol crystals (\u221278%). Cholesterol crystals are potent inducers of the NLRP3 inflammasome pathway and atorvastatin prevented its activation, which resulted in reduced expression of the pro-inflammatory cytokines interleukin (IL)-1\u03b2 (\u221261%) and IL-18 (\u221226%). Transcriptome analysis confirmed strong reducing effects of atorvastatin on inflammatory mediators, including NLRP3, NF\u03baB and TLR4. The present study demonstrates that atorvastatin reduces hepatic steatosis, inflammation and fibrosis and prevents cholesterol crystal formation, thereby precluding NLRP3 inflammasome activation. This may render atorvastatin treatment as an attractive approach to reduce NAFLD and prevent progression into NASH in dyslipidemic patients.<\/jats:p>","DOI":"10.3390\/ijms24097818","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T02:30:52Z","timestamp":1682476252000},"page":"7818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Atorvastatin Attenuates Diet-Induced Non-Alcoholic Steatohepatitis in APOE*3-Leiden Mice by Reducing Hepatic Inflammation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-6785","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Inia","sequence":"first","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"},{"name":"Department of Cardiology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-6311","authenticated-orcid":false,"given":"Geurt","family":"Stokman","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsbet J.","family":"Pieterman","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-943X","authenticated-orcid":false,"given":"Martine C.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-0897","authenticated-orcid":false,"given":"Aswin L.","family":"Menke","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-9037","authenticated-orcid":false,"given":"Lars","family":"Verschuren","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0248-4008","authenticated-orcid":false,"given":"Martien P. M.","family":"Caspers","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1684-1894","authenticated-orcid":false,"given":"Martin","family":"Giera","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-8359","authenticated-orcid":false,"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"},{"name":"Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-8446","authenticated-orcid":false,"given":"Anita M.","family":"van den Hoek","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-1596","authenticated-orcid":false,"given":"Hans M. G.","family":"Princen","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/hep.29466","article-title":"Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease","volume":"67","author":"Estes","year":"2018","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154170","DOI":"10.1016\/j.metabol.2020.154170","article-title":"Complications, morbidity and mortality of nonalcoholic fatty liver disease","volume":"111","author":"Mantovani","year":"2020","journal-title":"Metabolism"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0021-9150(02)00316-7","article-title":"Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus","volume":"166","author":"Huisman","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein","volume":"359","author":"Ridker","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1161\/01.CIR.0000086460.55494.AF","article-title":"Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: Evidence for antiinflammatory effects of rosuvastatin","volume":"108","author":"Havekes","year":"2003","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1182\/blood-2003-11-3791","article-title":"Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro","volume":"103","author":"Kleemann","year":"2004","journal-title":"Blood"},{"key":"ref_7","first-page":"10","article-title":"Identifying the anti-inflammatory response to lipid lowering therapy: A position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology","volume":"115","author":"Badimon","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1097\/MCG.0b013e31819c392e","article-title":"A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial","volume":"43","author":"Nelson","year":"2009","journal-title":"J. Clin. Gastroenter."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.jhep.2015.05.006","article-title":"Statin use and non-alcoholic steatohepatitis in at risk individuals","volume":"63","author":"Dongiovanni","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1161\/ATVBAHA.107.142570","article-title":"Mouse Models for Atherosclerosis and Pharmaceutical Modifiers","volume":"27","author":"Zadelaar","year":"2007","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejphar.2015.03.089","article-title":"Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C\/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials","volume":"763","author":"Fiocco","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9727952","DOI":"10.1155\/2019\/9727952","article-title":"The APOE*3-Leiden Heterozygous Glucokinase Knockout Mouse as Novel Translational Disease Model for Type 2 Diabetes, Dyslipidemia, and Diabetic Atherosclerosis","volume":"2019","author":"Pouwer","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1194\/jlr.M053207","article-title":"PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE","volume":"55","author":"Ason","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1161\/hq1001.096651","article-title":"Raman Spectroscopic Evaluation of the Effects of Diet and Lipid-Lowering Therapy on Atherosclerotic Plaque Development in Mice","volume":"21","author":"Romer","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.jhep.2014.12.011","article-title":"Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE(\u2217)3Leiden mice","volume":"62","author":"Morrison","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/hep4.1042","article-title":"CAT-2003: A novel sterol regulatory element-binding protein inhibitor that reduces steatohepatitis, plasma lipids, and atherosclerosis in apolipoprotein E*3-Leiden mice","volume":"1","author":"Zimmer","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1161\/01.ATV.0000238348.05028.14","article-title":"Fenofibrate reduces atherogenesis in ApoE*3Leiden mice: Evidence for multiple antiatherogenic effects besides lowering plasma cholesterol","volume":"26","author":"Kooistra","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1194\/jlr.M051326","article-title":"Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin","volume":"55","author":"Pieterman","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1194\/jlr.RA119000419","article-title":"Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice","volume":"61","author":"Pouwer","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Edwards, J.E., and Moore, R.A. (2003). Statins in hypercholesterolaemia: A dose-specific meta-analysis of lipid changes in randomised, double blind trials. BMC Fam. Pract., 4.","DOI":"10.1186\/1471-2296-4-18"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/nature08938","article-title":"NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nature"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.jhep.2017.01.022","article-title":"NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice","volume":"66","author":"Mridha","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jacl.2011.06.013","article-title":"3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: A therapeutic controversy","volume":"5","author":"Tzefos","year":"2011","journal-title":"J. Clin. Lipidol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101816","DOI":"10.1016\/j.clinre.2021.101816","article-title":"Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis","volume":"46","author":"Fatima","year":"2021","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/bcp.14943","article-title":"Statin liver safety in non-alcoholic fatty liver disease: A systematic review and metanalysis","volume":"88","author":"Pastori","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1001\/jamacardio.2016.4700","article-title":"National Trends in Statin Use and Expenditures in the US Adult Population From 2002 to 2013: Insights From the Medical Expenditure Panel Survey","volume":"2","author":"Salami","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.clnu.2022.08.001","article-title":"Statins\u2019 efficacy in non-alcoholic fatty liver disease: A systematic review and meta-analysis","volume":"41","author":"Boutari","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1007\/s00535-010-0203-y","article-title":"Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: Clinical usefulness of AGEs as a biomarker for the attenuation of NASH","volume":"45","author":"Kimura","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_30","first-page":"CD008623","article-title":"Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis","volume":"12","author":"Eslami","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"530","DOI":"10.4254\/wjh.v10.i8.530","article-title":"Current status of imaging in nonalcoholic fatty liver disease","volume":"10","author":"Li","year":"2018","journal-title":"World J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1210\/jc.2017-00867","article-title":"Liver Safety of Statins in Prediabetes or T2DM and Nonalcoholic Steatohepatitis: Post Hoc Analysis of a Randomized Trial","volume":"102","author":"Bril","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1194\/jlr.M019927","article-title":"Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia","volume":"53","author":"Yin","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1161\/01.ATV.0000148866.29829.19","article-title":"Effect of Low Dose Atorvastatin Versus Diet-Induced Cholesterol Lowering on Atherosclerotic Lesion Progression and Inflammation in Apolipoprotein E*3\u2013Leiden Transgenic Mice","volume":"25","author":"Verschuren","year":"2005","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Morrison, M.C., Mulder, P., Stavro, P.M., Su\u00e1rez, M., Arola-Arnal, A., Van Duyvenvoorde, W., Kooistra, T., Wielinga, P.Y., and Kleemann, R. (2015). Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139196"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1161\/01.CIR.103.13.1778","article-title":"Acyl-CoA:Cholesterol Acyltransferase Inhibitor Avasimibe Reduces Atherosclerosis in Addition to Its Cholesterol-Lowering Effect in ApoE*3-Leiden Mice","volume":"103","author":"Delsing","year":"2001","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/00005344-200307000-00010","article-title":"Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice","volume":"42","author":"Delsing","year":"2003","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"376","DOI":"10.4093\/dmj.2016.40.5.376","article-title":"Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice","volume":"40","author":"Park","year":"2016","journal-title":"Diabetes Metab. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lastuvkova, H., Faradonbeh, F.A., Schreiberova, J., Hroch, M., Mokry, J., Faistova, H., Nova, Z., Hyspler, R., Sa, I.C.I., and Nachtigal, P. (2021). Atorvastatin Modulates Bile Acid Homeostasis in Mice with Diet-Induced Nonalcoholic Steatohepatitis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126468"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1089\/dna.2022.0581","article-title":"Therapeutic Potential of Resveratrol and Atorvastatin Following High-Fat Diet Uptake-Induced Nonalcoholic Fatty Liver Disease by Targeting Genes Involved in Cholesterol Metabolism and miR33","volume":"42","author":"Yarahmadi","year":"2023","journal-title":"DNA Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/liv.12033","article-title":"Rosuvastatin ameliorates high-fat and high-cholesterol diet-induced nonalcoholic steatohepatitis in rats","volume":"33","author":"Okada","year":"2013","journal-title":"Liver Int."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Da Silva Pereira, E.N.G., De Araujo, B.P., Rodrigues, K.L., Silvares, R.R., Martins, C.S.M., Flores, E.E.I., Fernandes-Santos, C., and Daliry, A. (2022). Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress. Nutrients, 14.","DOI":"10.3390\/nu14030716"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.metabol.2008.07.030","article-title":"Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia","volume":"57","author":"Hyogo","year":"2008","journal-title":"Metabolism"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1172\/JCI0216452","article-title":"Consequences of cellular cholesterol accumulation: Basic concepts and physiological implications","volume":"110","author":"Tabas","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/hep.26592","article-title":"NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice","volume":"59","author":"Wree","year":"2014","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1177\/1074248418776261","article-title":"Simvastatin Suppresses Interleukin I\u03b2 Release in Human Peripheral Blood Mononuclear Cells Stimulated With Cholesterol Crystals","volume":"23","author":"Boland","year":"2018","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1684\/ecn.2009.0162","article-title":"Pharmacological inhibitors of the mevalonate pathway activate pro-IL-1 processing and IL-1 release by human monocytes","volume":"20","author":"Massonnet","year":"2009","journal-title":"Eur. Cytokine Netw."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9337","DOI":"10.1074\/jbc.M513000200","article-title":"Active Metabolite of Atorvastatin Inhibits Membrane Cholesterol Domain Formation by an Antioxidant Mechanism","volume":"281","author":"Mason","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1042\/CS20130043","article-title":"NLRP3 inflammasome activation in coronary artery disease: Results from prospective and randomized study of treatment with atorvastatin or rosuvastatin","volume":"126","author":"Satoh","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.2337\/db14-1059","article-title":"Statin-Induced Insulin Resistance through Inflammasome Activation: Sailing between Scylla and Charybdis","volume":"63","author":"Mitchell","year":"2014","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3389\/fimmu.2013.00289","article-title":"Interleukin-18 and IL-18 Binding Protein","volume":"4","author":"Dinarello","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.jhep.2021.04.013","article-title":"Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis","volume":"75","author":"Ooi","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.ATV.0000067702.22390.20","article-title":"Increased Fecal Bile Acid Excretion in Transgenic Mice with Elevated Expression of Human Phospholipid Transfer Protein","volume":"23","author":"Post","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Liang, W., Menke, A.L., Driessen, A., Koek, G.H., Lindeman, J.H., Stoop, R., Havekes, L.M., Kleemann, R., and van den Hoek, A.M. (2014). Establishment of a General NAFLD Scoring System for Rodent Models and Comparison to Human Liver Pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115922"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-pathol-121808-102132","article-title":"Nonalcoholic Fatty Liver Disease: Pathology and Pathogenesis","volume":"5","author":"Tiniakos","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/eurheartj\/ehu319","article-title":"Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin","volume":"36","author":"Simic","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/HJH.0b013e32834ddd8e","article-title":"Aliskiren inhibits atherosclerosis development and improves plaque stability in APOE*3Leiden.CETP transgenic mice with or without treatment with atorvastatin","volume":"30","author":"Hoek","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1021\/jasms.1c00203","article-title":"A DMS Shotgun Lipidomics Workflow Application to Facilitate High-Throughput, Comprehensive Lipidomics","volume":"32","author":"Su","year":"2021","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16369","DOI":"10.1021\/acs.analchem.1c02826","article-title":"Cross-Laboratory Standardization of Preclinical Lipidomics Using Differential Mobility Spectrometry and Multiple Reaction Monitoring","volume":"93","author":"Ghorasaini","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/hep4.1270","article-title":"Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-\/-.Leiden Mice","volume":"2","author":"Morrison","year":"2018","journal-title":"Hepatol. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7818\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:23:12Z","timestamp":1760124192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":63,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24097818"],"URL":"https:\/\/doi.org\/10.3390\/ijms24097818","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,25]]}}}