Effect of 1-deoxynojirimycin on cholesterol efflux through ABCA1-LXR alpha pathway in 3T3-L1 adipocytes

Abstract

We aimed to investigate whether 1-deoxynojirimycin (DNJ) has effects on cholesterol efflux in adipocytes and modulates ABCA1 expression in high fat fed mice. Fully differentiated 3T3-L1 adipocytes were tested for the cytotoxicity of DNJ and cholesterol efflux into apoA1/HDL was then assessed. ABCA1 protein levels and nuclear abundance of LXR alpha were measured after the treatment of DNJ in differentiated 3T3-L1 adipocytes. The effects of 12 week DNJ supplementation on ABCA1 gene expression in epididymal adipose tissue of high fat (HF) fed mice were further evaluated. Overnight treatment of DNJ increased cholesterol efflux mediated with ApoA1 and HDL in 3T3-L1 adipocytes. DNJ increased the protein expression of ABCA1 gene and enhanced the nuclear presence of LXR alpha, the transcription factor for ABCA1 in 3T3-L1 adipocytes. DNJ supplementation for 12 weeks upregulated the expression of ABCA1 in epididymal adipose tissue in HF fed mice, however, the effect was not related to the increase in circulating HDL-cholesterol levels. Thus, DNJ appears to have a positive impact on the reverse cholesterol metabolism by activating the ABCA1 LXR alpha pathway and enhancing the cholesterol efflux. DNJ may decrease the risk of metabolic disorders related to abnormal regulation of reverse cholesterol transport. (C) 2013 Elsevier Ltd. All rights reserved.