Effects of Excessive Choline Administration on Cardiovascular Risk Factors and Hepatic Cholesterol Metabolism in Female SD Rats

Abstract

Choline has been considered to be linked to an increase of cardiovascular risk. It can be metabolized to trimethylamine by gut microbiota and further converted by hepatic flavin monooxygenase 3 (FMO3) to trimethylamine‐N‐oxide (TMAO) which is known to be a putative promoter of cardiovascular disease. However, the effects of excessive choline administration on the cardiovascular risk, especially in SD rats, have been little studied. The purpose of this study was to evaluate the effects of excessive choline administration on serum TMAO level, aortic wall thickness, and expression of hepatic genes responsible for cholesterol metabolism in female SD rats. Twenty female SD rats were fed AIN93‐G diet with or without various concentrations of choline chloride (1.5%, 2.25%, 3%) (w/w) in autoclaved water for 8 weeks. Aortic wall section of the rat was stained by hematoxylin and eosin. Serum TMAO and choline levels were determined by UPLC‐Synapt G2‐Si. Hepatic mRNA expression of FMO3, farnesoid X receptor (FXR), liver X receptor α (LXRα), sterol regulatory element‐binding protein 2 (SREBP‐2), cholesterol 7 alpha‐hydroxylase (CYP7A1), and low‐density lipoprotein receptor (LDLR) was determined by quantitative PCR. Serum TMAO level was significantly (p<0.05) higher in the rat fed 1.5% choline‐containing water (1.5C) than control group (25.03 ± 14.27 vs. 0.34 ± 0.35 μM). However, serum choline levels were not significantly (p>0.05) different (18.01 ± 7.15 vs. 23.13 ± 11.89 μM). Aortic wall of the 1.5C seemed to be thicker than the control group. Relative mRNA expression of CYP7A1 was down‐regulated in the 1.5C compared to the control group (0.32 ± 0.24 vs. 1.00 ± 0.56, p<0.05), whereas that of FXR was up‐regulated (1.59 ± 0.60 vs. 1.00 ± 0.39, p<0.05). However, mRNA expressions of hepatic FMO3, LDLR, LXRα, and SREBP‐2 were not significantly (p>0.05) different. Excessive choline administration seemed to be able to affect cardiovascular system in female SD rats via production of TMAO and regulation of CYP7A1 and FXR. Additional research about secondary bile acid produced by gut bacteria is needed.Support or Funding InformationThis research has been supported by National Research Foundation of Korea (NRF‐ 2017R1D1A1B03028407) funded by the Ministry of Education of Korea.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.