| Glucose regulates fatty acid binding protein interaction with lipids and peroxisome proliferator-activated receptor α. | |
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MedLine Citation:
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PMID: 20628144 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Heather A Hostetler; Madhumitha Balanarasimha; Huan Huang; Matthew S Kelzer; Alagammai Kaliappan; Ann B Kier; Friedhelm Schroeder |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-13 |
Journal Detail:
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Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-13 Completed Date: 2011-01-19 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 3103-16 Citation Subset: IM |
Affiliation:
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Departments of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus
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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:
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DK-41402/DK/NIDDK NIH HHS; DK-77573/DK/NIDDK NIH HHS; R00 DK077573-03/DK/NIDDK NIH HHS; R00 DK077573-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acid-Binding Proteins; 0/Fatty Acids; 0/PPAR alpha; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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