TY - JOUR T1 - ABCD2 Alters PPARα Signaling in Vitro, but Does Not Impair Responses to Fenofibrate Therapy in a Mouse Model of Diet-induced Obesity JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.114.092742 SP - mol.114.092742 AU - Xiaoxi Liu AU - Jingjing Liu AU - Shuang Liang AU - Agatha Schluter AU - Stephane Fourcade AU - Stella Aslibekyan AU - Aurora Onofre Pujol AU - Gregory Graf Y1 - 2014/01/01 UR - http://molpharm.aspetjournals.org/content/early/2014/08/14/mol.114.092742.abstract N2 - Fenofibrate is a PPARα ligand that has been widely used as a lipid lowering agent in the treatment of hypertriglyceridemia. ABCD2 (D2) is a peroxisomal long-chain acyl-CoA transporter that is highly induced by fenofibrate in the livers of mice. To determine if D2 is a modifier of fibrate responses, wild-type and D2 deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARα signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that knock-down of D2 modified genomic responses to fibrate treatment. We next evaluated the impact of D2 on effects of fibrates in a mouse model of diet-induced obesity. Fenofibrate treatment opposed the development of obesity, hypertriglyceridemia, and insulin resistance. However, these effects were unaffected by D2 genotype. We concluded that D2 can modulate genomic responses to fibrates, but that these effects are not sufficiently robust to alter the effects of fibrates on diet-induced obesity phenotypes. ER -