RT Journal Article
SR Electronic
T1 Cilostazol Improves HFD-induced Hepatic Steatosis by Upregulating Hepatic STAMP2 Expression Through AMPK
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.118.113217
DO 10.1124/mol.118.113217
A1 Yoo Jin Oh
A1 Hye Young Kim
A1 Mi Hwa Lee
A1 Sung Hwan Suh
A1 Yongmun Choi
A1 Tae-gyu Nam
A1 Woo Young Kwon
A1 Sang Yeop Lee
A1 Young Hyun Yoo
YR 2018
UL http://molpharm.aspetjournals.org/content/early/2018/10/26/mol.118.113217.abstract
AB Non-alcoholic fatty liver disease (NAFLD) is an increasingly studied condition that may progress to end-stage liver disease. Although NAFLD was first described in 1980, a complete understanding of the mechanism and causes of this disease is still lacking. A previous study suggested that STAMP2 may be a suitable target for treating NAFLD. In the current study, we, performing a focused drug screening, found that cilostazol could be a potential STAMP2 enhancer. Thus, we examined whether cilostazol alleviates NAFLD through STAMP2. The in vivo and in vitro pharmacological efficacies of cilostazol on STAMP2 expression and lipid accumulation were analyzed in NAFLD mice induced by high fat diet (HFD) and HepG2 cell lines treated by oleic acid (OA), respectively. Cilostazol increased the expression of STAMP2 protein in vivo and in vitro. Cilostazol also dampened the STAMP2 downregulation caused by the HFD and by oleic acid (OA) in vivo and in vitro, respectively. Cilostazol activated AMPK (AMP-activated protein kinase) in vivo and in vitro, and AMPK functions upstream of STAMP2, and reverted downregulation of STAMP2 expression through AMPK in NAFLD model. Cilostazol ameliorates hepatic steatosis by enhancing hepatic STAMP2 expression through AMPK. Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD.