Increased expression of ATP-binding cassette transporter A1 by cilostazol may be a possible mechanism for its protective effect against hepatic steatosis

Bong-Soo Cha; Tae Sun Park; Byung Hun Jeon; Yong-Ho Lee; Mi Ra Yun; Byung Wan Lee; Eun Seok Kang; Hyun Chul Lee

doi:10.1530/endoabs.37.EP596

EP596

Prev Next

Section Contents Cite

Endocrine Abstracts (2015) 37 EP596 | DOI: 10.1530/endoabs.37.EP596

ECE2015 Eposter Presentations Obesity and cardiovascular endocrinology (108 abstracts)

Increased expression of ATP-binding cassette transporter A1 by cilostazol may be a possible mechanism for its protective effect against hepatic steatosis

Bong-Soo Cha ¹ , Tae Sun Park ² , Byung Hun Jeon ¹ , Yong-Ho Lee ¹ , Mi Ra Yun ¹ , Byung Wan Lee ¹ , Eun Seok Kang ¹ & Hyun Chul Lee ¹

Err

Author affiliations View ePoster Download ePoster

¹Yonsei University College of Medicine, Seoul, Republic of Korea; ²Chonbuk National University Medical School, Jeonju, Republic of Korea.

Objective: Cilostazol, a selective inhibitor of phosphodiesterase 3, which has been widely used in patients with atherosclerotic diseases, is known to have additional beneficial effects on dyslipidemia. ATP-binding cassette transporter A1 (ABCA1) plays a critical role in the regulation of intracellular cholesterol levels in hepatocytes. We aimed to investigate the effect of Cilostazol on hepatic steatosis and its underlying mechanism related to ABCA1.

Methods: Male C57BL/6 mice were randomly divided into three groups: i) fed normal chow diet with vehicle. ii) fed high-fat diet (HFD) with vehicle. iii) fed HFD with Cilostazol. Cilostazol (30 mg/kg) was orally administered once daily for 9 weeks. Oral glucose tolerance test was done and liver tissues were examined. HepG2 cells were also used as an in vitro model by incubating with saturated fatty acid (palmitate) in the presence or absence of Cilostazol.

Results: In HFD-fed mice, Cilostazol treatment significantly decreased hepatic fat and liver weight. Cilostazol-treated mice also showed improved glucose tolerance and decreased levels of serum LDL, VLDL and total cholesterol. The expression of ABCA1 was significantly increased in the liver of cilostazol-treated mice by 2.4-folds (P<0.05) compared to HFD-fed control mice. In palmitate-treated HepG2 cells, lipid accumulation was significantly decreased after treatment with Cilostazol. Palmitate reduced the expression of ABCA1, which was restored with Cilostazol treatment by 1.3-folds (P<0.05). The HDL-cholesterol levels in the cell cultured media were also increased, while intracellular LDL and VLDL-cholesterol levels were decreased in HepG2 cells treated with palmitate and cilostazol compared to those with palmitate only.

Conclusion: Our results showed that cilostazol ameliorated hepatic steatosis by increasing ABCA1 expression in the hepatocytes. This implicates that cilostazol may have a beneficial role in the treatment of non-alcoholic fatty liver disease.