ABCD2 alters peroxisome proliferator-activated receptor α signaling in vitro, but does not impair responses to fenofibrate therapy in a mouse model of diet-induced obesity

Xiaoxi Liu, Jingjing Liu, Shuang Liang, Agatha Schlüter, Stephane Fourcade, Stella Aslibekyan, Aurora Pujol, Gregory A. Graf

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) a 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 whether 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 knockdown 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.

Original languageEnglish
Pages (from-to)505-513
Number of pages9
JournalMolecular Pharmacology
Volume86
Issue number5
DOIs
StatePublished - Nov 1 2014

Bibliographical note

Publisher Copyright:
© 2014 by The American Society for Pharmacology and Experimental Therapeutics.

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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