| First Author | Oishi K | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 401 |
| Issue | 2 | Pages | 313-8 |
| PubMed ID | 20854792 | Mgi Jnum | J:165845 |
| Mgi Id | MGI:4838684 | Doi | 10.1016/j.bbrc.2010.09.060 |
| Citation | Oishi K, et al. (2010) PPARalpha deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPARgamma activation in the liver. Biochem Biophys Res Commun 401(2):313-8 |
| abstractText | An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor alpha (PPARalpha) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPARalpha-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPARalpha-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPARalpha target genes such as Cyp4A10 and FGF21 was damped in PPARalpha-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPARalpha-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPARalpha activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPARgamma and its coactivator PCG-1alpha were more effectively induced in PPARalpha-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPARgamma antagonist, in both WT and PPARalpha-null mice. PPARgamma activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression in the fatty liver. |
