ArticleThe Journal of biological chemistry2006
Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 85 citations in OpenAlex.
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- Serum trimethylamine-N-oxide and gut microbiome alterations are associated with cholesterol deposition in the liver of laying hens fed with rapeseed meal.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Article
- Gut-restricted apical sodium-dependent bile acid transporter inhibitor attenuates alcohol-induced liver steatosis and injury in mice.Alcoholism, clinical and experimental research · 2021Article
- Effects of Bile Acids on Growth Performance and Lipid Metabolism during Chronic Heat Stress in Broiler Chickens.Animals : an open access journal from MDPI · 2021Article
- Stress can attenuate hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in mice with nonalcoholic steatohepatitis.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Bile Acid Toxicity and Protein Kinases.Advances in experimental medicine and biology · 2021Article
- Depletion of hepatic forkhead box O1 does not affect cholelithiasis in male and female mice.The Journal of biological chemistry · 2020Article
- Glucose-6-Phosphate Regulates Hepatic Bile Acid Synthesis in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review.Nutrients · 2019Review
- Therapeutic Roles of Bile Acid Signaling in Chronic Liver Diseases.Journal of clinical and translational hepatology · 2018Review
- Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018Review
- FoxO transcription factors are required for hepatic HDL cholesterol clearance.The Journal of clinical investigation · 2018Article
- Osteopontin regulates the cross-talk between phosphatidylcholine and cholesterol metabolism in mouse liver.Journal of lipid research · 2017Article
- FOXO transcription factors in non-alcoholic fatty liver disease.Liver research (Beijing, China) · 2017Article
- PKCβ: Expanding role in hepatic adaptation of cholesterol homeostasis to dietary fat/cholesterol.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Insulin Resistance is Associated With Total Bile Acid Level in Type 2 Diabetic and Nondiabetic Population: A Cross-Sectional Study.Medicine · 2016Observational
- Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression.The Biochemical journal · 2015Article
- Modulation of Hepatic Protein Kinase Cβ Expression in Metabolic Adaptation to a Lithogenic Diet.Cellular and molecular gastroenterology and hepatology · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Bile acid synthesis and pool size increases in diabetes, whereas insulin inhibits bile acid synthesis. The objective of this study is to elucidate the mechanism of insulin regulation of cholesterol 7alpha-hydroxylase gene expression in human hepatocytes. Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. Insulin may play a major role in the regulation of bile acid synthesis and dyslipidemia in diabetes.
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Registered trials
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