| Human urinary metabolomic profile of PPARalpha induced fatty acid beta-oxidation. | |
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MedLine Citation:
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PMID: 19569716 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with increased fatty acid catabolism and is commonly targeted for the treatment of hyperlipidemia. To identify latent, endogenous biomarkers of PPARalpha activation and hence increased fatty acid beta-oxidation, healthy human volunteers were given fenofibrate orally for 2 weeks and their urine was profiled by UPLC-QTOFMS. Biomarkers identified by the machine learning algorithm random forests included significant depletion by day 14 of both pantothenic acid (>5-fold) and acetylcarnitine (>20-fold), observations that are consistent with known targets of PPARalpha including pantothenate kinase and genes encoding proteins involved in the transport and synthesis of acylcarnitines. It was also concluded that serum cholesterol (-12.7%), triglycerides (-25.6%), uric acid (-34.7%), together with urinary propylcarnitine (>10-fold), isobutyrylcarnitine (>2.5-fold), (S)-(+)-2-methylbutyrylcarnitine (5-fold), and isovalerylcarnitine (>5-fold) were all reduced by day 14. Specificity of these biomarkers as indicators of PPARalpha activation was demonstrated using the Ppara-null mouse. Urinary pantothenic acid and acylcarnitines may prove useful indicators of PPARalpha-induced fatty acid beta-oxidation in humans. This study illustrates the utility of a pharmacometabolomic approach to understand drug effects on lipid metabolism in both human populations and in inbred mouse models. |
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Authors:
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Andrew D Patterson; Ondrej Slanar; Kristopher W Krausz; Fei Li; Constance C Höfer; Frantisek Perlík; Frank J Gonzalez; Jeffrey R Idle |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of proteome research Volume: 8 ISSN: 1535-3893 ISO Abbreviation: J. Proteome Res. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-04 Completed Date: 2009-12-24 Revised Date: 2010-09-02 |
Medline Journal Info:
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Nlm Unique ID: 101128775 Medline TA: J Proteome Res Country: United States |
Other Details:
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Languages: eng Pagination: 4293-300 Citation Subset: IM |
Affiliation:
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Algorithms Analysis of Variance Animals Antilipemic Agents / pharmacology Artificial Intelligence Biological Markers / urine Carnitine / analogs & derivatives, urine Chromatography, High Pressure Liquid Fatty Acids / analysis, metabolism, urine* Female Humans Male Mass Spectrometry Metabolome / drug effects Metabolomics / methods* Mice Mice, Inbred C57BL PPAR alpha / urine* Pantothenic Acid / urine Procetofen / pharmacology Urine / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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Z01 BC005562-20/BC/NCI NIH HHS; Z01 BC005708-16/BC/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antilipemic Agents; 0/Biological Markers; 0/Fatty Acids; 0/PPAR alpha; 49562-28-9/Procetofen; 541-15-1/Carnitine; 79-83-4/Pantothenic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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