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Increased expression of ATP-binding cassette transporter A1 (ABCA1) as a possible mechanism for the protective effect of cilostazol against hepatic steatosis

Authors
 Byung Hun Jeon  ;  Yong-ho Lee  ;  Mi Ra Yun  ;  Soo Hyun Kim  ;  Byung Wan Lee  ;  Eun Seok Kang  ;  Hyun Chul Lee  ;  Bong-Soo Cha 
Citation
 Metabolism: Clinical and Experimental, Vol.64(11) : 1444-1453, 2015 
Journal Title
 Metabolism: Clinical and Experimental 
ISSN
 0026-0495 
Issue Date
2015
MeSH
ATP Binding Cassette Transporter 1/genetics ; ATP Binding Cassette Transporter 1/metabolism* ; Animals ; Apoptosis/drug effects ; Diet, High-Fat ; Fatty Liver/prevention & control* ; Hep G2 Cells ; Hepatocytes/drug effects ; Hepatocytes/pathology ; Humans ; Lipids/blood ; Male ; Mice ; Mice, Inbred C57BL ; Phosphodiesterase 3 Inhibitors/pharmacology* ; RNA, Small Interfering/genetics ; Tetrazoles/pharmacology*
Keywords
ABCA1 ; Cilostazol ; Dyslipidemia ; Hepatic steatosis
Abstract
OBJECTIVE: Cilostazol, a phosphodiesterase 3, has been widely used in patients with arterial disease and is known to have additional beneficial effects on dyslipidemia. However, the effect of cilostazol on hepatic steatosis has not been fully elucidated. We investigated the effect of cilostazol on hepatic ABCA1 expression and hepatic steatosis in diet-induced obesity mice model. METHODS: Hepatic ABCA1 expression and lipid accumulation were analyzed in HepG2 cell lines treated with cilostazol. Male C57BL/6 mice were randomly divided into three groups: (1) fed normal chow diet with vehicle; (2) fed high-fat diet (HFD) with vehicle; (3) fed HFD with cilostazol. Cilostazol (30mg/kg) was orally administered once daily for 9weeks. RESULTS: Cilostazol significantly enhanced ABCA1 expression and restored ABCA1 expression reduced by palmitate in HepG2 cells. Cilostazol treatment ameliorated lipid accumulation induced by palmitate, and this effect was diminished when ABCA1 or LRP1 was silenced by small interference RNA. After silencing of LRP1, ABCA1 expression was decreased in HepG2 cells. Cilostazol significantly enhanced hepatic ABCA1 expression and decreased hepatic fat in HFD-fed mice. Hepatic expression of cleaved caspase-3 and PARP1 was also decreased in HFD-fed mice treated with cilostazol. CONCLUSIONS: Cilostazol ameliorated hepatic steatosis and increased ABCA1 expression in the hepatocytes. Enhancing ABCA1 expression with cilostazol represents a potential therapeutic avenue for treatment of hepatic steatosis.
Full Text
http://www.sciencedirect.com/science/article/pii/S0026049515001948
DOI
10.1016/j.metabol.2015.07.014
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141698
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