| First Author | Martens K | Year | 2008 |
| Journal | Biochim Biophys Acta | Volume | 1781 |
| Issue | 11-12 | Pages | 694-702 |
| PubMed ID | 18773970 | Mgi Jnum | J:142427 |
| Mgi Id | MGI:3821508 | Doi | 10.1016/j.bbalip.2008.07.010 |
| Citation | Martens K, et al. (2008) Coordinate induction of PPARalpha and SREBP2 in multifunctional protein 2 deficient mice. Biochim Biophys Acta 1781(11-12):694-702 |
| abstractText | Mice with inactivation of the D-specific multifunctional protein 2 (MFP2), a crucial enzyme of peroxisomal beta-oxidation, develop multiple pathologies in diverse tissues already starting in the postnatal period. Gene expression profiling performed on liver of 2-day-old pups revealed up-regulation of PPARalpha responsive genes in knockout mice. Surprisingly, also genes involved in cholesterol biosynthesis were markedly induced. Real-time PCR confirmed the induction of PPARalpha target genes and of HMGCR and SREBP2, both involved in cholesterol synthesis, in lactating and in adult MFP2 knockout mice. In accordance, the rate of cholesterol biosynthesis was significantly increased in liver of knockout mice but the hepatic cholesterol concentration was unaltered. In MFP2/PPARalpha double knockout mice, up-regulations of SREBP2 and HMGCR were markedly attenuated. These data demonstrate a tight interrelationship between induction of PPARalpha by endogenous ligands and up-regulation of genes of cholesterol biosynthesis through increased expression of SREBP2. |
