Document Detail


Glucose regulates fatty acid binding protein interaction with lipids and peroxisome proliferator-activated receptor α.
MedLine Citation:
PMID:  20628144     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-α (PPARα), 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 PPARα. 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 PPARα transcriptional activity.
Authors:
Heather A Hostetler; Madhumitha Balanarasimha; Huan Huang; Matthew S Kelzer; Alagammai Kaliappan; Ann B Kier; Friedhelm Schroeder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-13
Journal Detail:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-13     Completed Date:  2011-01-19     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3103-16     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / drug effects
Animals
Cell Nucleus / drug effects,  metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Fatty Acid-Binding Proteins / chemistry,  metabolism*
Fatty Acids / chemistry,  metabolism
Glucose / metabolism,  pharmacology*
Lipid Metabolism / drug effects*
Mice
PPAR alpha / chemistry,  metabolism*
Protein Binding / drug effects
Protein Structure, Secondary / drug effects
Rats
Grant Support
ID/Acronym/Agency:
DK-41402/DK/NIDDK NIH HHS; DK-77573/DK/NIDDK NIH HHS; R00 DK077573/DK/NIDDK NIH HHS; R00 DK077573-03/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acid-Binding Proteins; 0/Fatty Acids; 0/PPAR alpha; IY9XDZ35W2/Glucose
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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