Cholesterol-induced non-alcoholic fatty liver disease and atherosclerosis aggravated by systemic inflammation

Eung Ju Kim, Baek-Hui Kim, Hong Seog Seo, Yong Jik Lee, Hyun Hee Kim, Hyun Hwa Son, Man Ho Choi

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Article numbere97841
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - 2014 Jun 5

Fingerprint

fatty liver
atherosclerosis
Liver
Atherosclerosis
aorta
inflammation
Cholesterol
cholesterol
Inflammation
liver
Aorta
lesions (animal)
cholesteryl esters
Toll-Like Receptor 4
Cholesterol Esters
foam cells
receptors
Tunica Intima
New Zealand White rabbit
hypercholesterolemia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cholesterol-induced non-alcoholic fatty liver disease and atherosclerosis aggravated by systemic inflammation. / Kim, Eung Ju; Kim, Baek-Hui; Seo, Hong Seog; Lee, Yong Jik; Kim, Hyun Hee; Son, Hyun Hwa; Choi, Man Ho.

In: PLoS One, Vol. 9, No. 6, e97841, 05.06.2014.

Research output: Contribution to journalArticle

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