| First Author | Fan CY | Year | 1998 |
| Journal | J Biol Chem | Volume | 273 |
| Issue | 25 | Pages | 15639-45 |
| PubMed ID | 9624157 | Mgi Jnum | J:48180 |
| Mgi Id | MGI:1266915 | Doi | 10.1074/jbc.273.25.15639 |
| Citation | Fan CY, et al. (1998) Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism. J Biol Chem 273(25):15639-45 |
| abstractText | Peroxisomal beta-oxidation system consists of four consecutive reactions to preferentially metabolize very long chain fatty acids. The first step of this system, catalyzed by acyl-CoA oxidase (AOX), converts fatty acyl-CoA to 2-trans-enoyl-CoA. Herein, we show that mice deficient in AOX exhibit steatohepatitis, increased hepatic H2O2 levels, and hepatocellular regeneration, leading to a complete reversal of fatty change by 6 to 8 months of age. The liver of AOX-/- mice with regenerated hepatocytes displays profound generalized spontaneous peroxisome proliferation and increased mRNA levels of genes that are regulated by peroxisome proliferator-activated receptor alpha (PPARalpha). Hepatic adenomas and carcinomas develop in AOX-/- mice by 15 months of age due to sustained activation of PPARalpha. These observations implicate acyl-CoA and other putative substrates for AOX, as biological ligands for PPARalpha; thus, a normal AOX gene is indispensable for the physiological regulation of PPARalpha. |
