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

Several studies showed that activation of PPARγ induces lipogenesis [38] [39] [40] . Since we previously showed that SREBP-1c and FAS mRNA expressions were increased in H-apoD Tg mice liver [15] , we measured the mRNA levels of key lipogenic enzymes including LXRα, a transcription factor that induces lipogenic gene transcription [66] [67] [68] [69] [70] . We did not observe any change in the mRNA levels of ACC, SCD1, DGAT and LXRα. We also observed an elevation of AMPK expression. The increased expression of AMPKα is consistent with a recent study reporting that CD36 increases AMPK expression through the action of both PPARγ and PGC-1α [71] . Consequently, AMPKα phosphorylation is higher in the liver of Tg mice, resulting in increased phosphorylation and inhibition of ACC [72] . Interestingly, Mao et al [73] showed that inhibition of ACC1 in mouse liver induces expression of FAS explaining why FAS expression is increased in our conditions. However, by directly measuring de novo lipogenesis in vivo using 3 H 2 O, we showed the over-expression of H-apoD has no significant effect on de novo lipid synthesis in 1-year-old animals. A similar observation was made in 3-month-old mice (data not shown).