ArticleJCI insight2018
Bile acids regulate cysteine catabolism and glutathione regeneration to modulate hepatic sensitivity to oxidative injury.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The trial behind it
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
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- Untargeted Metabolomics Reveals Metabolic Perturbations in Community-Dwelling Elderly Exposed to PMMetabolites · 2026Article
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Does Gamma-Glutamyl Transpeptidase Serum Level Play a Role as a Prognostic Marker in Biliary Atresia, an Immune-Mediated Cholangiopathy in Children?Journal of clinical medicine · 2025Article
- Hepatocyte and adipocyte CDO1-mediated intracellular cysteine catabolism differentially modulates diet-induced obesity and fatty liver in mice.bioRxiv : the preprint server for biology · 2025Article
- Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.Hepatology (Baltimore, Md.) · 2025Review
- Bile acid sequestrant inhibits gluconeogenesis via inducing hepatic cysteine dioxygenase type 1 to reduce cysteine availability.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Metabolome-wide associations with short-term exposure to PMFrontiers in public health · 2025Article
- Deletion of hepatocyte cysteine dioxygenase type 1, a bile acid repressed gene, enhances glutathione synthesis and ameliorates acetaminophen hepatotoxicity.Biochemical pharmacology · 2024Article
- Bile acids regulation of cellular stress responses in liver physiology and diseases.eGastroenterology · 2024Article
- The role of bacteria in gallstone formation.Folia microbiologica · 2024Review
- The oral administration ofmSphere · 2024Article
- Dynamics of blood Taurine concentration and its correlation with nutritional and physiological status during the fattening period of Japanese black cattle.Journal of animal science · 2024Article
- Thermal proteome profiling unveils protein targets of deoxycholic acid in living neuronal cells.Advanced biotechnology · 2023Article
- Divergence in aerobic capacity influences hepatic and systemic metabolic adaptations to bile acid sequestrant and short-term high-fat/sucrose feeding in rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples.Journal of pharmaceutical analysis · 2023Article
- Programmed Cell Death Pathways in Cholangiocarcinoma: Opportunities for Targeted Therapy.Cancers · 2023Review
- Bile acids profile and redox status in healthy infants.Pediatric research · 2023Article
- Cysteine dioxygenase type 1 (CDO1): Its functional role in physiological and pathophysiological processes.Genes & diseases · 2023Review
- Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage.BMC genomics · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Bile acids are signaling molecules that critically control hepatocellular function. Disrupted bile acid homeostasis may be implicated in the pathogenesis of chronic liver diseases. Glutathione is an important antioxidant that protects the liver against oxidative injury. Various forms of liver disease share the common characteristics of reduced cellular glutathione and elevated oxidative stress. This study reports a potentially novel physiological function of bile acids in regulating hepatic sulfur amino acid and glutathione metabolism. We found that bile acids strongly inhibited the cysteine dioxygenase type-1-mediated (CDO1-mediated) cysteine catabolic pathway via a farnesoid X receptor-dependent mechanism. Attenuating this bile acid repressive effect depleted the free cysteine pool and reduced the glutathione concentration in mouse liver. Upon acetaminophen challenge, cholestyramine-fed mice showed impaired hepatic glutathione regeneration capacity and markedly worsened liver injury, which was fully prevented by N-acetylcysteine administration. These effects were recapitulated in CDO1-overexpressing hepatocytes. Findings from this study support the importance of maintaining bile acid homeostasis under physiological and pathophysiological conditions, as altered hepatic bile acid signaling may negatively impact the antioxidant defense mechanism and sensitivity to oxidative injury. Furthermore, this finding provides a possible explanation for the reported mild hepatotoxicity associated with the clinical use of bile acid sequestrants in human patients.
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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.