Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism
Recently, trimethylamine-N-oxide (TMAO) plasma levels have been proved to be associated with atherosclerosis development. Among the targets aimed to ameliorating atherosclerotic lesions, inducing bile acid synthesis to eliminate excess cholesterol in body is an effective way. Individual bile acid as...
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Published in | Lipids in health and disease Vol. 17; no. 1; p. 286 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BioMed Central Ltd
19.12.2018
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
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Summary: | Recently, trimethylamine-N-oxide (TMAO) plasma levels have been proved to be associated with atherosclerosis development. Among the targets aimed to ameliorating atherosclerotic lesions, inducing bile acid synthesis to eliminate excess cholesterol in body is an effective way. Individual bile acid as endogenous ligands for the nuclear receptor has differential effects on regulating bile acid metabolism. It is unclear whether bile acid profiles are mechanistically linked to TMAO-induced development of atherosclerosis.
Male apoE
mice were fed with control diet containing 0.3% TMAO for 8 weeks. Aortic lesion development and serum lipid profiles were determined. Bile acid profiles in bile, liver and serum were measured by liquid chromatographic separation and mass spectrometric detection (LC-MS). Real-time PCRs were performed to analyze mRNA expression of genes related to hepatic bile acid metabolism.
The total plaque areas in the aortas strongly increased 2-fold (P < 0.001) in TMAO administration mice. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) in TMAO group were also significantly increased by 25.5% (P = 0.044), 31.2% (P = 0.006), 28.3% (P = 0.032), respectively. TMAO notably changed bile acid profiles, especially in serum, the most prominent inductions were tauromuricholic acid (TMCA), deoxycholic acid (DCA) and cholic acid (CA). Mechanically, TMAO inhibited hepatic bile acid synthesis by specifically repressing the classical bile acid synthesis pathway, which might be mediated by activation of small heterodimer partner (SHP) and farnesoid X receptor (FXR).
These findings suggested that TMAO accelerated aortic lesion formation in apoE
mice by altering bile acid profiles, further activating nuclear receptor FXR and SHP to inhibit bile acid synthesis by reducing Cyp7a1 expression. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1476-511X 1476-511X |
DOI: | 10.1186/s12944-018-0939-6 |