An Experimental Study Of The Effect Of ACC2-inhibitor On NAFLD

Objectives: To explore the effect of ACC2-inhibitor on NAFLD and relatedmechanisms.Methods: Treat human liver cells HL-7702(ucp2) with long chain fat emulsioninjection for 48 hours in order to develope cell models of non-alcoholic fattyliver(NAFL). Then the previous NAFL models were exposed to oleic acid for 30 minto get NASH cell models. And then treat NAFLD cell models with ACC-inhibitor,observe the growing conditions of the cells, as well as TG content in cells andbiochemical data like AST in the medium. ACC2 activity was determined bymeasuring the incorporation of [14C]bicarbonate into mylonyl-CoA andmylonyl-CoA was determined by HPLD and CPTI activity was determined as well.Results: Culture cells with the medium including long chain fat emulsioninjection (0.5μl/ml) previously described, 48 hours later we found that TGcontent in cells increased remarkably(p＜0.01), while AST leaking out into themedium varied little (p＞0.05). Thus we developed cell models of NAFL. When theprevous NAFL cells were exposed to oleic acid, AST leaking out into the mediumincreased markedly(p＜0.01) and NASH cell models in vivo were thus established.24 hours after treated with ACC2 inhibitor, TG content in NAFL cells decreased alot(p＜0.05), while ACC activity and mylonyl-CoA content in cellsdecreased (p＜0.01), and CPTI activity increased (p＜0.01) after applyment of ACC2I.We also found that when exposed to oleic acid, AST leaking into the mediumdecreased (p＜0.01) in ACC2I experimental NAFL cellsConclusion: Cell models of NAFLD in vivo can be built in short term by long chainfat emulsion injection and oleic acid. While ACC2 inhibitor may improve the coursethat FFAs come into NAFL cells, and increaseβ-oxidation in mitochondria ofhepatocytes.