ArticleExperimental & molecular medicine2011
Insulin-dependent suppression of cholesterol 7α-hydroxylase is a possible link between glucose and cholesterol metabolisms.
Article in Experimental & molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
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- Hepatic protein kinase Cβ antagonizing p38American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Bile acids: potential links to overweight/obesity and androgen levels in pubertal girls.Frontiers in endocrinology · 2025Article
- Role of bile acids in overweight and obese children and adolescents.Frontiers in endocrinology · 2022Review
- Depletion of hepatic forkhead box O1 does not affect cholelithiasis in male and female mice.The Journal of biological chemistry · 2020Article
- Postprandial Dyslipidemia, Hyperinsulinemia, and Impaired Gut Peptides/Bile Acids in Adolescents with Obesity.The Journal of clinical endocrinology and metabolism · 2020Article
- Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review.Drug design, development and therapy · 2020Review
- Insulin Fused to Apolipoprotein A-I Reduces Body Weight and Steatosis in DB/DB Mice.Frontiers in pharmacology · 2020Article
- Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review.Nutrients · 2019Review
- Extracting proteins involved in disease progression using temporally connected networks.BMC systems biology · 2018Article
- Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity.Scientific reports · 2018Article
- The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- FOXO transcription factors in non-alcoholic fatty liver disease.Liver research (Beijing, China) · 2017Article
- TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice.Gut · 2017Article
- Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice.Toxicology and applied pharmacology · 2013Article
- Soaping up type 2 diabetes with bile acids?: the link between glucose and bile acid metabolism in humans tightens: quality matters!Diabetes · 2013Article
- Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6.Experimental & molecular medicine · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol 7α-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin- Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.
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