| First Author | Petrescu AD | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1831 |
| Issue | 8 | Pages | 1412-25 |
| PubMed ID | 23747828 | Mgi Jnum | J:202533 |
| Mgi Id | MGI:5519990 | Doi | 10.1016/j.bbalip.2013.05.008 |
| Citation | Petrescu AD, et al. (2013) High glucose potentiates L-FABP mediated fibrate induction of PPARalpha in mouse hepatocytes. Biochim Biophys Acta 1831(8):1412-25 |
| abstractText | Although liver fatty acid binding protein (L-FABP) binds fibrates and PPARalpha in vitro and enhances fibrate induction of PPARalpha in transformed cells, the functional significance of these findings is unclear, especially in normal hepatocytes. Studies with cultured primary mouse hepatocytes show that: 1) At physiological (6mM) glucose, fibrates (bezafibrate, fenofibrate) only weakly activated PPARalpha transcription of genes in LCFA beta-oxidation; 2) High (11-20mM) glucose, but not maltose (osmotic control), significantly potentiated fibrate-induction of mRNA of these and other PPARalpha target genes to increase LCFA beta-oxidation. These effects were associated with fibrate-mediated redistribution of L-FABP into nuclei-an effect prolonged by high glucose-but not with increased de novo fatty acid synthesis from glucose; 3) Potentiation of bezafibrate action by high glucose required an intact L-FABP/PPARalpha signaling pathway as shown with L-FABP null, PPARalpha null, PPARalpha inhibitor-treated WT, or PPARalpha-specific fenofibrate-treated WT hepatocytes. High glucose alone in the absence of fibrate was ineffective. Thus, high glucose potentiation of PPARalpha occurred through FABP/PPARalpha rather than indirectly through other PPARs or glucose induced signaling pathways. These data indicated L-FABP's importance in fibrate-induction of hepatic PPARalpha LCFA beta-oxidative genes, especially in the context of high glucose levels. |
