| First Author | Palladino EN | Year | 2017 |
| Journal | J Lipid Res | Volume | 58 |
| Issue | 2 | Pages | 317-324 |
| PubMed ID | 28007964 | Mgi Jnum | J:239304 |
| Mgi Id | MGI:5828311 | Doi | 10.1194/jlr.M069740 |
| Citation | Palladino EN, et al. (2017) Peroxisome proliferator-activated receptor-alpha accelerates alpha-chlorofatty acid catabolism. J Lipid Res 58(2):317-324 |
| abstractText | alpha-Chlorofatty aldehydes are generated from myeloperoxidase-derived HOCl targeting plasmalogens, and are subsequently oxidized to alpha-chlorofatty acids (alpha-ClFAs). The catabolic pathway for alpha-ClFA is initiated by omega-oxidation. Here, we examine PPAR-alpha activation as a mechanism to increase alpha-ClFA catabolism. Pretreating both HepG2 cells and primary mouse hepatocytes with the PPAR-alpha agonist, pirinixic acid (Wy 14643), increased the production of alpha-chlorodicarboxylic acids (alpha-ClDCAs) in cells treated with exogenous alpha-ClFA. Additionally, alpha-ClDCA production in Wy 14643-pretreated wild-type mouse hepatocytes was accompanied by a reduction in cellular free alpha-ClFA. The dependence of PPAR-alpha-accelerated alpha-ClFA catabolism was further demonstrated by both impaired metabolism in mouse PPAR-alpha-/- hepatocytes and decreased clearance of plasma alpha-ClFA in PPAR-alpha-/- mice. Furthermore, Wy 14643 treatments decreased plasma 2-chlorohexadecanoic acid levels in wild-type mice. Additional studies showed that alpha-ClFA increases PPAR-alpha, PPAR-delta, and PPAR-gamma activities, as well as mRNA expression of the PPAR-alpha target genes, CD36, CPT1a, Cyp4a10, and CIDEC. Collectively, these results indicate that PPAR-alpha accelerates important pathways for the clearance of alpha-ClFA, and alpha-ClFA may, in part, accelerate its catabolism by serving as a ligand for PPAR-alpha. |
