Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
1998-11-6
pubmed:databankReference
pubmed:abstractText
Fatty acid transport protein (FATP) was identified by expression cloning strategies (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436) and shown by transfection analysis to catalyze the transfer of long-chain fatty acids across the plasma membrane of cells. It is expressed highly in tissues exhibiting rapid fatty acid metabolism such as skeletal muscle, heart, and adipose. FATP mRNA levels are down-regulated by insulin in cultured 3T3-L1 adipocytes and up-regulated by nutrient depletion in murine adipose tissue (Man, M. Z., Hui, T. Y., Schaffer, J. E., Lodish, H. F., and Bernlohr, D. A. (1996) Mol. Endocrinol. 10, 1021-1028). To determine the molecular mechanism of insulin regulation of FATP transcription, we have isolated the murine FATP gene and its 5'-flanking sequences. The FATP gene spans approximately 16 kilobases and contains 13 exons, of which exon 2 is alternatively spliced. S1 nuclease and RNase protection assays revealed the presence of multiple transcription start sites; the DNA sequence upstream of the predominant transcription start sites lacks a typical TATA box. By transient transfection assays in 3T3-L1 adipocytes, the inhibitory action of insulin on FATP transcription was localized to a cis-acting element with the sequence 5'-TGTTTTC-3' from -1347 to -1353. This sequence is very similar to the insulin response sequence found in the regulatory region of other genes negatively regulated by insulin such as those encoding phosphoenolpyruvate carboxykinase, tyrosine aminotransferase, and insulin-like growth factor-binding protein 1. Fluorescence in situ hybridization analysis revealed that the murine FATP gene is localized to chromosome 8, band 8B3.3. Interestingly, this region of chromosome 8 contains a cluster of three other genes important for fatty acid homeostasis, lipoprotein lipase, the mitochondrial uncoupling protein 1 (UCP1) and sterol regulatory element-binding protein 1. These results characterize the murine FATP gene and its insulin responsiveness as well as present a framework for future studies of its role in lipid metabolism, obesity, and type II diabetes mellitus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27420-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:9765271-Adipocytes, pubmed-meshheading:9765271-Alternative Splicing, pubmed-meshheading:9765271-Animals, pubmed-meshheading:9765271-Base Sequence, pubmed-meshheading:9765271-Carrier Proteins, pubmed-meshheading:9765271-Chromosome Mapping, pubmed-meshheading:9765271-Cloning, Molecular, pubmed-meshheading:9765271-Exons, pubmed-meshheading:9765271-Fatty Acid Transport Proteins, pubmed-meshheading:9765271-Fatty Acids, pubmed-meshheading:9765271-Gene Expression Regulation, pubmed-meshheading:9765271-In Situ Hybridization, Fluorescence, pubmed-meshheading:9765271-Insulin, pubmed-meshheading:9765271-Introns, pubmed-meshheading:9765271-Membrane Proteins, pubmed-meshheading:9765271-Membrane Transport Proteins, pubmed-meshheading:9765271-Mice, pubmed-meshheading:9765271-Molecular Sequence Data, pubmed-meshheading:9765271-Promoter Regions, Genetic, pubmed-meshheading:9765271-Protein Binding, pubmed-meshheading:9765271-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:9765271-Sequence Analysis, DNA, pubmed-meshheading:9765271-Transcription, Genetic
pubmed:year
1998
pubmed:articleTitle
Characterization of the murine fatty acid transport protein gene and its insulin response sequence.
pubmed:affiliation
Department of Biochemistry, University of Minnesota, St. Paul, Minnesota 55108, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.