Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPAR? and Fatty Acid Uptake

Labrie, Marilyne; Lalonde, Simon; Najyb, Ouafa; Thiery, Maxime; Daneault, Caroline; Des Rosiers, Chrisitne; Rassart, Eric; Mounier, Catherine

In the liver of H-apoD Tg mice, we observed a strong increase in PPARγ expression associated with an activation of its transcriptional activity. Interestingly, PPARγ and C/EBPα activate each other's expression maintaining a positive feedback loop for the development of an adipocyte like phenotype [20, 21, 59] . Complementing these data, we observed a slight increase in C/ EBPα expression while C/EBPβ remained unchanged. It is to note that the upregulation of C/ EBPα expression is minor. This could be explained by the fact that the hepatic steatosis progression in Tg mice is very slow and hence, the genes implicated are expected to be only slightly modulated. Furthermore, elevated PPARγ expression results in the increase of CD36 expression. However, the LPL and HSL levels remained constant at least at the mRNA level. Previous studies demonstrated that activation of PPARγ in the liver increases expression of LPL and CD36 [29, 30] however, in our model only the FA uptake is affected without any increase in lipoproteins hydrolysis. Similar observations associating increased CD36 expression and FA uptake were made in cardiac cells [60] .