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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Moore, David D. Park, Young Joo Strom, Stephen Lee, Yoon-kwang Li, Tiangang Ma, Huiyan Chiang, John Y. L. |
| Description | Author Affiliation: Li T ( Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, 4209 State Route 44, Rootstown, OH 44272, USA.) |
| Abstract | The conversion of cholesterol to bile acids is the major pathway for cholesterol catabolism. Bile acids are metabolic regulators of triglycerides and glucose metabolism in the liver. This study investigated the roles of FoxO1 in the regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression in primary human hepatocytes. Adenovirus-mediated expression of a phosphorylation defective and constitutively active form of FoxO1 (FoxO1-ADA) inhibited CYP7A1 mRNA expression and bile acid synthesis, while siRNA knockdown of FoxO1 resulted in a approximately 6-fold induction of CYP7A1 mRNA in human hepatocytes. Insulin caused rapid exclusion of FoxO1 from the nucleus and resulted in the induction of CYP7A1 mRNA expression, which was blocked by FoxO1-ADA. In high fat diet-fed mice, CYP7A1 mRNA expression was repressed and inversely correlated to increase hepatic FoxO1 mRNA expression and FoxO1 nuclear retention. In conclusion, our current study provides direct evidence that FoxO1 is a strong repressor of CYP7A1 gene expression and bile acid synthesis. Impaired regulation of FoxO1 may cause down-regulation of CYP7A1 gene expression and contribute to dyslipidemia in insulin resistance. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 10 |
| Volume Number | 1791 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2009-10-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Cholesterol 7-alpha-Hydroxylase Antagonists & Inhibitors Dietary Fats Administration & Dosage Pharmacology Feeding Behavior Drug Effects Forkhead Transcription Factors Metabolism Hepatocytes Enzymology Adenoviridae Genetics Animals Bile Acids And Salts Biosynthesis Cell Line, Tumor Cell Nucleus Down-Regulation Gene Expression Regulation, Enzymologic Gene Knockdown Techniques Gene Transfer Techniques Insulin Insulin Resistance Mice Mice, Inbred C57BL RNA Interference RNA, Messenger Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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