Liver expresses high levels of two proteins with high affinity for long chain fatty acids (LCFAs): liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2). Real-time confocal microscopy of cultured primary hepatocytes from gene ablated (L-FABP, SCP-2/SCP-x, and L-FABP/SCP-2/SCP-x null) mice showed that the loss of L-FABP reduced cellular uptake of NBD-stearic acid (fluorescent saturated LCFA analogue) by about 50%. Importantly, nuclear targeting of the LCFA was enhanced when L-FABP was upregulated (SCP-2/SCP-x null), but significantly reduced when L-FABP was ablated (L-FABP null) thus impacting LCFA nuclear targeting. These effects were not associated with a net decrease in the expression of key membrane proteins involved in LCFA or glucose transport. Since hepatic LCFA uptake and metabolism is closely linked to that of glucose, the effect of glucose on L-FABP-mediated LCFA uptake and nuclear targeting was examined. Increasing concentrations of glucose not only decreased cellular LCFA uptake but more so LCFA nuclear targeting. Loss of L-FABP exacerbated the decrease in LCFA nuclear targeting while the loss of SCP-2 reduced the glucose effect, resulting in enhanced LCFA nuclear targeting as compared to the control. Simply, ablation of L-FABP decreases LCFA uptake and even more so its nuclear targeting.
- fatty acids
- Copyright © 2011, American Journal of Physiology- Gastrointestinal and Liver Physiology