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: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE

Original Publication: Amsterdam : Elsevier Pub. Co.

Bile Acids and Salts/*metabolism ; Diabetes Mellitus/*metabolism ; Lipid Metabolism/*physiology ; Metabolome/*genetics ; Obesity/*metabolism; Animals ; Bile Acids and Salts/genetics ; Cholesterol 7-alpha-Hydroxylase/genetics ; Cholesterol 7-alpha-Hydroxylase/metabolism ; Diabetes Mellitus/genetics ; Diet, High-Fat/methods ; Female ; Glucose/genetics ; Glucose/metabolism ; Homeostasis ; Insulin Resistance ; Intestinal Mucosa/metabolism ; Liver/metabolism ; Male ; Metabolomics/methods ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Obesity/genetics ; Rats ; Signal Transduction ; Taurocholic Acid/analogs & derivatives ; Taurocholic Acid/genetics ; Taurocholic Acid/metabolism

Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-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-β-muricholic acid (T-β-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-β-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12α-hydroxylated bile acids and increasing intestinal T-β-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.
(Copyright © 2014 Elsevier B.V. All rights reserved.)

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R01 DK044442 United States DK NIDDK NIH HHS; R37 DK058379 United States DK NIDDK NIH HHS; United States ImNIH Intramural NIH HHS

Keywords: CYP7A1; bile acid metabolism; farnesoid X receptor (FXR); lipidomics; tauro-β-muricholic acid

0 (Bile Acids and Salts)
25696-60-0 (tauromuricholic acid)
5E090O0G3Z (Taurocholic Acid)
EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase)
EC 1.14.14.23 (Cyp7a1 protein, mouse)
IY9XDZ35W2 (Glucose)

Date Created: 20140507 Date Completed: 20150129 Latest Revision: 20220330

20221213

PMC4219936

10.1016/j.bbalip.2014.04.008

24796972