| RRC ID |
52145
|
| 著者 |
Fujita K, Iguchi Y, Une M, Watanabe S.
|
| タイトル |
Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.
|
| ジャーナル |
Lipids
|
| Abstract |
The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.
|
| 巻・号 |
52(4)
|
| ページ |
335-344
|
| 公開日 |
2017-4-1
|
| DOI |
10.1007/s11745-017-4242-5
|
| PII |
10.1007/s11745-017-4242-5
|
| PMID |
28315136
|
| MeSH |
Animals
Cell Line
Chenodeoxycholic Acid / metabolism
Cholic Acids
Deoxycholic Acid / metabolism
Gene Expression Regulation / drug effects
Lipogenesis / drug effects*
Liver / metabolism*
Male
Mice
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
Receptors, Cytoplasmic and Nuclear / metabolism*
Sterol Regulatory Element Binding Protein 1 / genetics*
Ursodeoxycholic Acid / administration & dosage*
Ursodeoxycholic Acid / pharmacology
|
| IF |
1.919
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
Hepa 1-6(RCB1638) |
