1.The effects of soluble epoxide hydrolase inhibitors on cholesterol efflux in adipocytes
Yun JIANG ; Danyan XU ; Shuiping ZHAO ; Yingwang LIU ; Tingting ZHAO ; Jianqing DU
Chinese Journal of Internal Medicine 2011;50(3):235-239
Objective To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes. Methods 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimilated with 100μg/L LPS after starved for 24 hours, then tAUCB in various concentrations(1 ,10,50,100 μmol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARy) antagonist GW9662 (5 μmol/L).0μmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARγ and adenosine triphosphate binding cassette transporter Al (ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARγand ABCA1 in cells were detected by Western blot, the efflux rates of 3H-cholesterol in cells were detected by means of liquid scintillation counter. Results tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10,50,100 μmol/L tAUCB, cholesterol efflux rates were (5.93±0.66) %, (7.40 ± 0. 43) %, (8. 30 ±0. 34)% ,(9.77±0.42)% respectively, there were significant difference after treated by 10-100 μmol/L tAUCB compared with control(5.67±0.17)%(P<0.05). With the concentration of tAUCB increased,ABCA1, PPAR mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARγ and ABCA1 in adipocytes. Conclusions tAUCB could up-regulate PPARγ expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.