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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743791 | PMC |
http://dx.doi.org/10.1016/j.bbalip.2009.05.004 | DOI Listing |
J Ethnopharmacol
January 2025
Department of Pharmacology, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, 712046, People's Republic of China. Electronic address:
Ethnopharmacological Relevance: Dioscorea bulbifera L. (DBL) was a traditional Chinese medicine commonly used to treat goitre and cancer. Nevertheless, its clinical application may lead to liver injury.
View Article and Find Full Text PDFDig Dis Sci
December 2024
Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China.
Background: NXT629, a PPAR-alpha antagonist, exerts widespread effects in many diseases; however, its function and relevant mechanism in cholesterol gallstones (CG) remain largely unknown.
Methods: Male C57BL/6 J mice were fed a regular diet or lithogenic diet (LD), followed by treatment with intraperitoneal injection of NXT629. H&E staining was performed to analyze hepatic pathological changes, and Oil red O staining was conducted to detect lipid accumulation.
Antioxidants (Basel)
October 2024
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Iron overload is a common complication in various chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD). Lipid and bile acid metabolism disorders are regarded as crucial hallmarks of NAFLD. However, effects of iron accumulation on lipid and bile acid metabolism are not well understood.
View Article and Find Full Text PDFJ Anim Sci
January 2024
Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan.
Taurine, biosynthesized from methionine or cysteine in the liver, plays a crucial regulatory role in bile acid conjugation, antioxidant effects, and glucose and cholesterol metabolism. This may influence the metabolic changes associated with fat accumulation in beef cattle. However, the physiological role of taurine in this species has not been fully elucidated.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
November 2024
Changsha Research and Development Center on Obstetric and Gynecologic Traditional Chinese Medicine Preparation, NHC Key Laboratory of Birth Defects Research, Prevention and Treatment, Hunan Provincial Maternal and Child Health Care Hospital, No. 53 Xiangchun Road, Kaifu District, Changsha, 410008, Hunan, China.
Background And Objectives: Hypertensive nephropathy (HN) has become one of the main causes of end-stage renal disease. Drug combination therapy is a common clinical treatment for HN. However, the impact of HN on drug-metabolizing enzymes and transporters, which may lead to drug-drug interactions (DDIs) and even trigger toxic side effects, remains unclear.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!