Dual effects of oxidized low-density lipoprotein on LXR-ABCA1-apoA-I pathway in 3T3-L1 cells.

Background: The adipocyte has been proven to recognize and degrade oxidized low-density lipoprotein (oxLDL), while cholesterol efflux from adipocytes to clear excess cholesterol loaded by oxLDL is essential to maintain its normal function. Thus, it is intriguing to explore the effects of oxLDL on cholesterol efflux in adipocytes.

Methods: Fully differentiated 3T3-L1 cells were incubated in the medium containing various concentrations of oxLDL (0 to 50 microg/mL) for 8 or 24 h. 10 micromol/L 22(R)-hydroxycholesterol was exposed to preconditioned adipocytes with 25 microg/mL oxLDL for 24 h. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate adipocytes mRNA expression. Cholesterol efflux rate was determined through measuring release of radioactivity from (3)H-cholesterol prelabeled cells into medium containing apolipoprotein A-I (apoA-I).

Results: Low concentrations of oxLDL caused a significant increase in apoA-I-mediated cholesterol efflux via enhancement of ATP binding cassette transporter A1 (ABCA1) pathway, whereas higher concentrations were incapable. In adipocytes preincubated with 25 microg/mL oxLDL for 24 h, 22(R)-hydroxycholesterol could increase ABCA1 and LXR* mRNA levels and apoA-I-mediated cholesterol efflux.

Conclusion: OxLDL has dual effects on ABCA1 pathway in adipocytes. It depends on the concentration and exposure time. The new action of low levels of oxLDL may provide further understanding to its atheroprotective effects.