ArticleHepatology (Baltimore, Md.)2019
Hepatic Autophagy Deficiency Compromises Farnesoid X Receptor Functionality and Causes Cholestatic Injury.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Dual Immune Lineage Activation Underlies Systemic Immunopathology in Acute-on-Chronic Liver Failure.The American journal of pathology · 2026Article
- Polystyrene nanoplastics induce hepatic steatosis by disrupting autophagic degradation of NCoR1 and suppressing PPARα-mediated fatty acid oxidation.Journal of nanobiotechnology · 2026Article
- Magnesium isoglycyrrhizinate ameliorates acetaminophen-induced acute liver injury with hyperglycaemia by modulating autophagy and oxidative stress in liver-resident macrophages.Frontiers in pharmacology · 2026Article
- The therapeutic potential of botanicals: how medicinal plants targeting autophagy can reverse metabolic-associated fatty liver disease.Frontiers in pharmacology · 2026Review
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- Autophagy regulates MK-2206-induced LDL receptor expression and cholesterol efflux pathways.PloS one · 2025Article
- Transcriptional changes impact hepatic proteome in autophagy-impaired liver.FEBS open bio · 2024Article
- Mitochondria at the Crossroads of Cholestatic Liver Injury: Targeting Novel Therapeutic Avenues.Journal of clinical and translational hepatology · 2024Review
- Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.Antioxidants (Basel, Switzerland) · 2024Article
- Bile acids regulation of cellular stress responses in liver physiology and diseases.eGastroenterology · 2024Article
- Loss of SLC27A5 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis via Unconjugated Cholic Acid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Autophagy modulates physiologic and adaptive response in the liver.Liver research (Beijing, China) · 2023Review
- Vine tea extract ameliorated acute liver injury by inhibiting hepatic autophagy and reversing abnormal bile acid metabolism.Heliyon · 2023Article
- NRF2 transcriptionally regulates Caspase-11 expression to activate HMGB1 release by Autophagy-deficient hepatocytes.Cell death discovery · 2023Article
- Impaired hepatic autophagy exacerbates hepatotoxin induced liver injury.Cell death discovery · 2023Article
- FXR deficiency in hepatocytes disrupts the bile acid homeostasis and inhibits autophagy to promote liver injury in Schistosoma japonicum-infected mice.PLoS neglected tropical diseases · 2022Article
- Knockout of farnesoid X receptor gene aggravates cisplatin-induced kidney injury.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- NRF2 Activation in Autophagy Defects Suppresses a Pharmacological Transactivation of the Nuclear Receptor FXR.Antioxidants (Basel, Switzerland) · 2022Article
- The autophagic protein p62 is a target of reactive aldehydes in human and murine cholestatic liver disease.PloS one · 2022Article
- Therapeutic regulation of autophagy in hepatic metabolism.Acta pharmaceutica Sinica. B · 2022Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
Autophagy is important for hepatic homeostasis, nutrient regeneration, and organelle quality control. We investigated the mechanisms by which liver injury occurred in the absence of autophagy function. We found that mice deficient in autophagy because of the lack of autophagy-related gene 7 or autophagy-related gene 5, key autophagy-related genes, manifested intracellular cholestasis with increased levels of serum bile acids, a higher ratio of tauromuricholic acid/taurocholic acid in the bile, increased hepatic bile acid load, abnormal bile canaliculi, and altered expression of hepatic transporters. In determining the underlying mechanism, we found that autophagy sustained and promoted the basal and up-regulated expression of farnesoid X receptor (Fxr) in the fed and starved conditions, respectively. Consequently, expression of Fxr and its downstream genes, particularly bile salt export pump, and the binding of FXR to the promoter regions of these genes, were suppressed in autophagy-deficient livers. In addition, codeletion of nuclear factor erythroid 2-related factor 2 (Nrf2) in autophagy deficiency status reversed the FXR suppression. Furthermore, the cholestatic injury of autophagy-deficient livers was reversed by enhancement of FXR activity or expression, or by Nrf2 deletion. Conclusion: Together with earlier reports that FXR can suppress autophagy, our findings indicate that autophagy and FXR form a regulatory loop and deficiency of autophagy causes abnormal FXR functionality, leading to the development of intracellular cholestasis and liver injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.