| Metabolomics reveals an essential role for peroxisome proliferator-activated receptor α in bile acid homeostasis. | |
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MedLine Citation:
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PMID: 22665165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that regulates fatty acid transport and metabolism. Previous studies revealed that PPARα can affect bile acid metabolism; however, the mechanism by which PPARα regulates bile acid homeostasis is not understood. In this study, an ultraperformance liquid chromatography coupled with electrospray ionization qua dru pole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics approach was used to profile metabolites in urine, serum, and bile of wild-type and Ppara-null mice following cholic acid (CA) dietary challenge. Metabolomic analysis showed that the levels of several serum bile acids, such as CA (25-fold) and taurocholic acid (16-fold), were significantly increased in CA-treated Ppara-null mice compared with CA-treated wild-type mice. Phospholipid homeostasis, as revealed by decreased serum lysophos phati dylcholine (LPC) 16:0 (1.6-fold) and LPC 18:0 (1.6-fold), and corticosterone metabolism noted by increased urinary excretion of 11β-hydroxy-3,20-dioxopregn-4-en-21-oic acid (20-fold) and 11β,20α-dihydroxy-3-oxo-pregn-4-en-21-oic acid (3.6-fold), were disrupted in CA-treated Ppara-null mice. The hepatic levels of mRNA encoding transporters Abcb11, Abcb4, Abca1, Abcg5, and Abcg8 were diminished in Ppara-null mice, leading to the accumulation of bile acids in the liver during the CA challenge. These observations revealed that PPARα is an essential regulator of bile acid biosynthesis, transport, and secretion. |
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Authors:
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Fei Li; Andrew D Patterson; Kristopher W Krausz; Naoki Tanaka; Frank J Gonzalez |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2012-06-04 |
Journal Detail:
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Title: Journal of lipid research Volume: 53 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-16 Completed Date: 2012-11-23 Revised Date: 2013-04-16 |
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: 1625-35 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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Animals Bile Acids and Salts / biosynthesis, metabolism*, secretion Biological Transport / drug effects, genetics Cholesterol / metabolism Cholic Acids / pharmacology Corticosterone / metabolism Diet Gene Deletion Homeostasis* / drug effects, genetics Male Metabolomics* Mice PPAR alpha / deficiency, genetics, metabolism* Phospholipids / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/Cholic Acids; 0/PPAR alpha; 0/Phospholipids; 50-22-6/Corticosterone; 57-88-5/Cholesterol |
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