ArticleMolecular and cellular biology2012
Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1α/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
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- Chlorogenic acid attenuates pyrrolizidine alkaloid-induced liver injury through modulation of the SIRT1/FXR signaling pathway.Chinese medicine · 2025Article
- Study on the molecular mechanisms of rifaximin in the treatment of non‑alcoholic steatohepatitis based on theMolecular medicine reports · 2025Article
- Regulation of hepatic Sirt1 expression and lipid metabolism through TNF receptor signaling.Frontiers in immunology · 2025Article
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats.Current research in pharmacology and drug discovery · 2024Article
- The role of SIRT1-FXR signaling pathway in valproic acid induced liver injury: a quantitative targeted metabolomic evaluation in epileptic children.Frontiers in pharmacology · 2024Article
- The Culprit Behind HBV-Infected Hepatocytes: NTCP.Drug design, development and therapy · 2024Review
- AQP3-mediated activation of the AMPK/SIRT1 signaling pathway curtails gallstone formation in mice by inhibiting inflammatory injury of gallbladder mucosal epithelial cells.Molecular medicine (Cambridge, Mass.) · 2023Article
- Human Hepatocyte Nuclear Factors (HNF1 and LXRb) Regulate CYP7A1 in HIV-Infected Black South African Women with Gallstone Disease: A Preliminary Study.Life (Basel, Switzerland) · 2023Article
- Role of Hepatocyte Transporters in Drug-Induced Liver Injury (DILI)-In Vitro Testing.Pharmaceutics · 2022Review
- Regulation of the HBV Entry Receptor NTCP and its Potential in Hepatitis B Treatment.Frontiers in molecular biosciences · 2022Review
- Obesity and Gallstones.Visceral medicine · 2021Review
- SIRT1 alleviates hepatic ischemia-reperfusion injury via the miR-182-mediated XBP1/NLRP3 pathway.Molecular therapy. Nucleic acids · 2021Article
- Prevention of Cholesterol Gallstone Formation byFood science of animal resources · 2021Article
- Ethanol Exposure Attenuates Immune Response in Sepsis via Sirtuin 2 Expression.Alcoholism, clinical and experimental research · 2021Article
- Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages.Frontiers in pharmacology · 2021Article
- Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders.Frontiers in endocrinology · 2021Review
- Paeoniflorin Protects against ANIT-Induced Cholestatic Liver Injury in Rats via the Activation of SIRT1-FXR Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Copy number variants in lipid metabolism genes are associated with gallstones disease in men.European journal of human genetics : EJHG · 2020Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
SIRT1, a highly conserved NAD(+)-dependent protein deacetylase, is a key metabolic sensor that directly links nutrient signals to animal metabolic homeostasis. Although SIRT1 has been implicated in a number of hepatic metabolic processes, the mechanisms by which hepatic SIRT1 modulates bile acid metabolism are still not well understood. Here we report that deletion of hepatic SIRT1 reduces the expression of farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid homeostasis. We provide evidence that SIRT1 regulates the expression of FXR through hepatocyte nuclear factor 1α (HNF1α). SIRT1 deficiency in hepatocytes leads to decreased binding of HNF1α to the FXR promoter. Furthermore, we show that hepatocyte-specific deletion of SIRT1 leads to derangements in bile acid metabolism, predisposing the mice to development of cholesterol gallstones on a lithogenic diet. Taken together, our findings indicate that SIRT1 plays a vital role in the regulation of hepatic bile acid homeostasis through the HNF1α/FXR signaling pathway.
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