Glucose regulates fatty acid binding protein interaction with lipids and peroxisome proliferator-activated receptor α

Although the pathophysiology of diabetes is characterized by elevated levels of glucose and long-chain fatty acids (LCFA), nuclear mechanisms linking glucose and LCFA metabolism are poorly understood. As the liver fatty acid binding protein (L-FABP) shuttles LCFA to the nucleus, where L-FABP directly interacts with peroxisome proliferator-activated receptor-alpha (PPAR alpha), the effect of glucose on these processes was examined. In vitro studies showed that L-FABP strongly bound glucose and glucose-1-phosphate (K-d = 103 +/- 19 nM and K-d = 20 +/- 3 nM, respectively), resulting in altered L-FABP conformation, increased affinity for lipid ligands, and enhanced interaction with PPAR alpha. In living cells, glucose stimulated cellular uptake and nuclear localization of a nonmetabolizable fluorescent fatty acid analog (BODIPY C-16), particularly in the presence of L-FABP. These data suggest for the first time a direct role of glucose in facilitating L-FABP-mediated uptake and distribution of lipidic ligands to the nucleus for regulation of PPAR alpha transcriptional activity.-Hostetler, H. A., M. Balanarasimha, H. Huang, M. S. Kelzer, A. Kaliappan, A. B. Kier, and F. Schroeder. Glucose regulates fatty acid binding protein interaction with lipids and peroxisome proliferator-activated receptor alpha. J. Lipid Res. 2010. 51: 3103-3116.