Abstract
Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid-supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1. Hyodeoxycholic acid administration markedly changes the ratio of FXR-antagonist/FXR-agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration.
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Abbreviations
- ACC:
-
Acetyl-CoA carboxylase
- CE:
-
Cholesteryl ester
- CYP7a1:
-
Cytochrome P450 7a1
- FXR:
-
Farnesoid X receptor
- FAS:
-
Fatty acid synthase
- HMGCAR:
-
3-Hydroxy-3-methylglutaryl coenzyme-A reductase
- LCMS:
-
Liquid chromatography–mass spectrometry
- MUFA:
-
Monounsaturated fatty acid
- PL:
-
Phospholipid
- SCD1:
-
Stearoyl-CoA desaturase-1
- SOAT2:
-
Sterol-O-acyltransferase-2
- SREBP1c:
-
Sterol regulatory element binding protein 1c
- TAG:
-
Triglyceride
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Acknowledgments
This work was supported in part by a Grant-in-Aid in Regional Innovation R&D Program from the Ministry of Economy, Trade and Industry, Japan and by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Research Project Number: 23590873). The authors wish to thank Mr. Shunsuke Komado and Mr. Atsushi Yoneyama (University of Toyama) for their help in analyzing gene expression and fatty acid composition.
Conflict of interest
S.W. received financial support from Kokando Co., Ltd., Japan. K.F. has no conflict of interest directly relevant to the content of this article.
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Watanabe, S., Fujita, K. Dietary Hyodeoxycholic Acid Exerts Hypolipidemic Effects by Reducing Farnesoid X Receptor Antagonist Bile Acids in Mouse Enterohepatic Tissues. Lipids 49, 963–973 (2014). https://doi.org/10.1007/s11745-014-3947-y
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DOI: https://doi.org/10.1007/s11745-014-3947-y