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.

Title

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.

Creator

Qi Yunpeng; Jiang Changtao; Cheng Jie; Krausz Kristopher W; Li Tiangang; Ferrell Jessica M; Gonzalez Frank J; Chiang John Y L

Publisher

Biochimica et biophysica acta

Date

2015
2015-01

Description

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.

Subject

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

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

19–29

Issue

1

Volume

1851

Citation

Qi Yunpeng; Jiang Changtao; Cheng Jie; Krausz Kristopher W; Li Tiangang; Ferrell Jessica M; Gonzalez Frank J; Chiang John Y L, “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.,” NEOMED Bibliography Database, accessed May 7, 2021, https://neomed.omeka.net/items/show/3476.

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