Source:http://linkedlifedata.com/resource/pubmed/id/16702440
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2006-7-14
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| pubmed:abstractText |
Oleoylethanolamide (OEA) is an endogenous lipid mediator that reduces food intake, promotes lipolysis, and decreases body weight gain in rodents by activating peroxisome proliferator-activated receptor-alpha (PPAR-alpha). The biological effects of OEA are terminated by two intracellular lipid hydrolase enzymes, fatty-acid amide hydrolase and N-acylethanolamine-hydrolyzing acid amidase. In the present study, we describe OEA analogs that resist enzymatic hydrolysis, activate PPAR-alpha with high potency in vitro, and persistently reduce feeding when administered in vivo either parenterally or orally. The most potent of these compounds, (Z)-(R)-9-octadecenamide,N-(2-hydroxyethyl,1-methyl) (KDS-5104), stimulates transcriptional activity of PPAR-alpha with a half-maximal effective concentration (EC50) of 100 +/- 21 nM (n = 11). Parenteral administration of KDS-5104 in rats produces persistent dose-dependent prolongation of feeding latency and postmeal interval (half-maximal effective dose, ED50 = 2.4 +/- 1.8 mg kg(-1) i.p.; n = 18), as well as increased and protracted tissue exposure compared with OEA. Oral administration of the compound also results in a significant tissue exposure and reduction of food intake in free-feeding rats. These results suggest that the endogenous high-affinity PPAR-alpha agonist OEA may provide a scaffold for the discovery of novel orally active PPAR-alpha ligands.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Appetite Depressants,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Oleic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/oleoylethanolamide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
0022-3565
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
318
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
563-70
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:16702440-Animals,
pubmed-meshheading:16702440-Appetite Depressants,
pubmed-meshheading:16702440-Eating,
pubmed-meshheading:16702440-HeLa Cells,
pubmed-meshheading:16702440-Humans,
pubmed-meshheading:16702440-Hydrolysis,
pubmed-meshheading:16702440-Indicators and Reagents,
pubmed-meshheading:16702440-Male,
pubmed-meshheading:16702440-Mass Spectrometry,
pubmed-meshheading:16702440-Mice,
pubmed-meshheading:16702440-Mice, Inbred C57BL,
pubmed-meshheading:16702440-Models, Molecular,
pubmed-meshheading:16702440-Motor Activity,
pubmed-meshheading:16702440-Oleic Acids,
pubmed-meshheading:16702440-PPAR alpha,
pubmed-meshheading:16702440-Rats,
pubmed-meshheading:16702440-Rats, Wistar,
pubmed-meshheading:16702440-Receptors, Drug,
pubmed-meshheading:16702440-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:16702440-Spectroscopy, Fourier Transform Infrared
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| pubmed:year |
2006
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| pubmed:articleTitle |
Pharmacological characterization of hydrolysis-resistant analogs of oleoylethanolamide with potent anorexiant properties.
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| pubmed:affiliation |
Department of Pharmacology, 360 MSRII, University of California, Irvine, CA 92697-4625, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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