Objective      To determine the relationship between leptin and the intracellular fat metabolism in insulin-resistant liver cell models.       Methods      Insulin-resistant liver cell models (LO2-I) were generated from LO2 cells with long-term treatment of 1 μmol/L insulin. The LO2-I cells were then treated with leptin (0

50

100

and 250 μg/L) and/or 2 μmol/L leptin antagonist (leptin-A). The transcription of hepatic lipase (HL) and lipoprotein lipase (LPL) genes was determined by real-time PCR. The protein expression of HL and LPL was evaluated by Western blotting. Oil red-O staining was used to observe intracellular lipid accumulation in LO2-I cells.       Results      LO2 cells with long-term treatment of 1 μmol/L insulin showed a significant decrease in insulin treatment response

indicating insulin resistance. LO2-I cells had an expression decrease of HL and LPL on both mRNA and protein levels

as compared to LO2 cells. The mRNA and protein levels of HL and LPL were increased significantly after being treated with leptin for 24 h in the LO2-I cells. Meanwhile

the intracellular accumulation of lipid was also significantly reduced. Leptin antagonist inhibited the leptin-induced HL and LPL expression up-regulation and caused obvious intracellular lipid accumulation.       Conclusion      Leptin accelerates lipid metabolism by increasing LPL and HL expression at both mRNA and protein levels in gestational diabetes liver cell model.