The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis.

ABSTRACT: Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this work, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in hepatic DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid homeostasis. The Abcd3 KO mouse presents with increased hepatic long-chain DCAs, increased urine medium-chain DCAs, lipodystrophy, enhanced hepatic choleste

SUBMITTER: Ranea-Robles P 

PROVIDER: S-EPMC8578467 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature