Glucose regulates fatty acid binding protein interaction with lipids and peroxisome proliferator-activated receptor . uri icon

abstract

  • 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- (PPAR), 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. 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 transcriptional activity.

published proceedings

  • J Lipid Res

author list (cited authors)

  • Hostetler, H. A., Balanarasimha, M., Huang, H., Kelzer, M. S., Kaliappan, A., Kier, A. B., & Schroeder, F.

citation count

  • 36

complete list of authors

  • Hostetler, Heather A||Balanarasimha, Madhumitha||Huang, Huan||Kelzer, Matthew S||Kaliappan, Alagammai||Kier, Ann B||Schroeder, Friedhelm

publication date

  • November 2010