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

PPARα is activated by long chain fatty acid (LCFA) [74, 75] . We previously demonstrated that hepatic PPARα mRNA is increased in H-apoD Tg mice liver [15] . PPARα is a nuclear receptor that activates the transcription of several genes implicated in the mitochondrial β-oxidation of lipids [75] . Its elevated expression is associated with an increased expression of CPT1, the rate limiting-enzyme of the mitochondrial β-oxidation [76] . Since CPT-1 is normally inhibited by malonyl-CoA produced by ACC [77] , inhibition of ACC in the liver of H-apoD Tg mice is associated with an increased expression of CPT-1 strongly suggesting an activation of the β-oxidation. However, this increased expression is mild and does not appear sufficient to reverse the progression of the hepatic steatosis in the H-apoD Tg mice.