title: Increased expression of ATP-binding cassette transporter A1 (ABCA1) as a possible mechanism for the protective effect of cilostazol against 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 (30 mg/kg) was orally administered once daily for 9 weeks.
  
  
  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.
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byung Hun
authors.initials: BH
authors.lastname: Jeon
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yong-ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Yun
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byung Wan
authors.initials: BW
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address: bscha@yuhs.ac.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Cha
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077407:Cilostazol; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000517:prevention & control*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000077407:Cilostazol; D008055:Lipids; D058987:Phosphodiesterase 3 Inhibitors; D034741:RNA, Small Interfering; D013777:Tetrazoles; C577833:Abca1 protein, mouse
keywords: ABCA1; Cilostazol; Dyslipidemia; Hepatic steatosis