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Text
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<a href="http://doi.org/10.1016/j.bbalip.2014.04.008" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bbalip.2014.04.008</a>
Pages
19–29
Issue
1
Volume
1851
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Title
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Bile acid signaling in lipid metabolism: metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice.
Publisher
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Biochimica et biophysica acta
Date
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2015
2015-01
Subject
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Animals; bile acid metabolism; Bile Acids and Salts/genetics/*metabolism; Cholesterol 7-alpha-Hydroxylase/genetics/metabolism; CYP7A1; Diabetes Mellitus/genetics/*metabolism; Diet; farnesoid X receptor (FXR); Female; Glucose/genetics/metabolism; High-Fat/methods; Homeostasis; Inbred C57BL; Insulin Resistance; Intestinal Mucosa/metabolism; Lipid Metabolism/*physiology; lipidomics; Liver/metabolism; Male; Metabolome/*genetics; Metabolomics/methods; Mice; Obesity/genetics/*metabolism; Rats; Signal Transduction; tauro-beta-muricholic acid; Taurocholic Acid/analogs & derivatives/genetics/metabolism; Transgenic
Creator
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Qi Yunpeng; Jiang Changtao; Cheng Jie; Krausz Kristopher W; Li Tiangang; Ferrell Jessica M; Gonzalez Frank J; Chiang John Y L
Description
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Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-beta-muricholic acid (T-beta-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-beta-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12alpha-hydroxylated bile acids and increasing intestinal T-beta-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics.
Identifier
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<a href="http://doi.org/10.1016/j.bbalip.2014.04.008" target="_blank" rel="noreferrer noopener">10.1016/j.bbalip.2014.04.008</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2015
Animals
Bile acid metabolism
Bile Acids and Salts/genetics/*metabolism
Biochimica et biophysica acta
Cheng Jie
Chiang John Y L
Cholesterol 7-alpha-Hydroxylase/genetics/metabolism
CYP7A1
Department of Integrative Medical Sciences
Diabetes Mellitus/genetics/*metabolism
Diet
farnesoid X receptor (FXR)
Female
Ferrell Jessica M
Glucose/genetics/metabolism
Gonzalez Frank J
High-Fat/methods
Homeostasis
Inbred C57BL
Insulin Resistance
Intestinal Mucosa/metabolism
Jiang Changtao
Krausz Kristopher W
Li Tiangang
Lipid Metabolism/*physiology
lipidomics
Liver/metabolism
Male
Metabolome/*genetics
Metabolomics/methods
Mice
NEOMED College of Medicine
Obesity/genetics/*metabolism
Qi Yunpeng
Rats
Signal Transduction
tauro-beta-muricholic acid
Taurocholic Acid/analogs & derivatives/genetics/metabolism
Transgenic