Document Detail

Metabolomics reveals an essential role for peroxisome proliferator-activated receptor α in bile acid homeostasis.
MedLine Citation:
PMID:  22665165     Owner:  NLM     Status:  MEDLINE    
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.
Fei Li; Andrew D Patterson; Kristopher W Krausz; Naoki Tanaka; Frank J Gonzalez
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-06-04
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-16     Completed Date:  2012-11-23     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1625-35     Citation Subset:  IM    
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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MeSH Terms
Bile Acids and Salts / biosynthesis,  metabolism*,  secretion
Biological Transport / drug effects,  genetics
Cholesterol / metabolism
Cholic Acids / pharmacology
Corticosterone / metabolism
Gene Deletion
Homeostasis* / drug effects,  genetics
PPAR alpha / deficiency,  genetics,  metabolism*
Phospholipids / metabolism
Reg. No./Substance:
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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