title: Cholesterol-induced non-alcoholic fatty liver disease and atherosclerosis aggravated by systemic inflammation.
abstract: Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II-IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II-IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs.
authors.affiliation: Cardiovascular Center, Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Eung Ju
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Baek-hui
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; The Korea University-Korea Institute of Science and Technology (KU-KIST) Graduate School of Converging Science and Technology, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Hong Seog
authors.initials: HS
authors.lastname: Seo
authors.affiliation: Cardiovascular Center, Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yong Jik
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Cardiovascular Center, Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Hyun-Hwa
authors.initials: HH
authors.lastname: Son
authors.affiliation: Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Man Ho
authors.initials: MH
authors.lastname: Choi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002784:Cholesterol / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D002784:Cholesterol