System ( tm ) for BBA - Molecular and Cell Biology of Lipids

ABSTRACT Apolipoprotein M (apoM) is a novel apolipoprotein presented mostly in highdensity lipoprotein (HDL) in human plasma. Previously we have reported that both leptin and leptin receptor are essential for apoM expression in vivo. Expression of apoM is lower in the leptin deficient (ob/ob) mouse and leptin receptor deficient (db/db) mouse than in the normal mouse. In the present study, however, we demonstrated that supra-physiological concentrations of recombinant leptin significantly inhibited apoM transcription and secretion in the human hepatoma cell line, HepG2 cells. Both northern blotting and real-time RT-PCR were applied into the analyses of apoM mRNA levels, and compatible data were obtained. The inhibitory effect of leptin on apoM mRNA levels in HepG2 cells is dose dependent, i.e. 100 ng/mL of leptin decreased apoM mRNA levels by 30%, and 500 ng/mL of leptin decreased apoM mRNA levels about 50%. Even at a physiological concentration of leptin (10 ng/mL), apoM expression was decreased, and in parallel, secretion of apoM into the medium was also decreased. Furthermore, we examined apoAI, apoB and apoE by northern blotting analyses. The results demonstrated that leptin does not significantly influence expressions of apoAI, apoB and apoE in HepC2 cells, suggesting that leptin has a specific regulatory effect on hepatic apoM transcription and secretion in vitro. The mechanism on the contradictory effects of leptin on apoM expression in vivo and in vitro needs further investigation.