Jiang_2011_Zhonghua.Nei.Ke.Za.Zhi_50_235

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 stimulated with 100 microg/L LPS after starved for 24 hours, then tAUCB in various concentrations (1, 10, 50, 100 micromol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARgamma) antagonist GW9662 (5 micromol/L). 0 micromol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARgamma and adenosine triphosphate binding cassette transporter A1(ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARgamma and ABCA1 in cells were detected by Western blot, the efflux rates of (3)H-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 micromol/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 micromol/L tAUCB compared with control (5.67 +/- 0.17)% (P < 0.05).With the concentration of tAUCB increased, ABCA1, PPARgamma 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 PPARgamma and ABCA1 in adipocytes.
CONCLUSIONS: tAUCB could up-regulate PPARgamma expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.