| First Author | Petrescu AD | Year | 2013 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 304 |
| Issue | 3 | Pages | G241-56 |
| PubMed ID | 23238934 | Mgi Jnum | J:194850 |
| Mgi Id | MGI:5474907 | Doi | 10.1152/ajpgi.00334.2012 |
| Citation | Petrescu AD, et al. (2013) Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARalpha-regulated beta-oxidative enzymes. Am J Physiol Gastrointest Liver Physiol 304(3):G241-56 |
| abstractText | Liver fatty acid binding protein (L-FABP) is the major soluble protein that binds very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) in hepatocytes. However, nothing is known about L-FABP's role in n-3 PUFA-mediated peroxisome proliferator activated receptor-alpha (PPARalpha) transcription of proteins involved in long-chain fatty acid (LCFA) beta-oxidation. This issue was addressed in cultured primary hepatocytes from wild-type, L-FABP-null, and PPARalpha-null mice with these major findings: 1) PUFA-mediated increase in the expression of PPARalpha-regulated LCFA beta-oxidative enzymes, LCFA/LCFA-CoA binding proteins (L-FABP, ACBP), and PPARalpha itself was L-FABP dependent; 2) PPARalpha transcription, robustly potentiated by high glucose but not maltose, a sugar not taken up, correlated with higher protein levels of these LCFA beta-oxidative enzymes and with increased LCFA beta-oxidation; and 3) high glucose altered the potency of n-3 relative to n-6 PUFA. This was not due to a direct effect of glucose on PPARalpha transcriptional activity nor indirectly through de novo fatty acid synthesis from glucose. Synergism was also not due to glucose impacting other signaling pathways, since it was observed only in hepatocytes expressing both L-FABP and PPARalpha. Ablation of L-FABP or PPARalpha as well as treatment with MK886 (PPARalpha inhibitor) abolished/reduced PUFA-mediated PPARalpha transcription of these genes, especially at high glucose. Finally, the PUFA-enhanced L-FABP distribution into nuclei with high glucose augmentation of the L-FABP/PPARalpha interaction reveals not only the importance of L-FABP for PUFA induction of PPARalpha target genes in fatty acid beta-oxidation but also the significance of a high glucose enhancement effect in diabetes. |
