Liver X Receptor Agonist T0901317 Downregulates ApoM Expression In Vivo And In Vitro

Objective: In the present study, we investigated the effect of liver X receptor (LXR) agonist T0901317 on regulation of apolipoprotein (apo) M.Methods: Comparing administration of 0.9% saline, DMSO and different dosages of LXR agonist T0901317 (10 mg/kg and 100 mg/kg) to male C57BL-6J mice by oral administration for 7 days, the protein levels of apoM in mice serum was estimated by dot blotting analysis. 1μM and 25μM of T0901317 and different concentrations of 9-cis retinoic acid (9-cis RA) (10 nM and 100 nM) were given to HepG2 cells, apoM mRNA expression was determined by real-time RT-PCR.Results: Serum apoM levels in mice administrated with 100 mg/kg T0901317 were reduced 12.29% compared with that of DMSO group (P < 0.05). ApoM mRNA levels at 25μM T0901317 (1μM=0.48 mg/L) was significantly lower (37.12%) than that in the untreated cells (P < 0.001). Compared with control, 25μM T0901317 together with 100 nM RA decreased apoM mRNA expression by 64.95% (P < 0.001). Conclusions: In the present study, we clearly demonstrated that LXR agonist T0901317 significantly downregulates apoM mRNA expression in a dose-dependent manner, which indicates apoM is another novel target gene regulated by LXR. Results of the combination of RA and T0901317 showed additive activity, which suggests that apoM expression can be modulated by LXR/RXR pathway.