ArticleCellular and molecular gastroenterology and hepatology2018
FXR-Mediated Cortical Cholesterol Accumulation Contributes to the Pathogenesis of Type A Hepatic Encephalopathy.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.Translational neurodegeneration · 2026Review
- Dysregulation of bile acid signal transduction causes neurological dysfunction in cirrhosis rats.World journal of hepatology · 2025Article
- Elderly mice with history of acetaminophen intoxication display worsened cognitive impairment and persistent elevation of astrocyte and microglia burden.Scientific reports · 2024Article
- Gut Microbiota-Metabolite-Brain Axis Reconstitution Reverses Sevoflurane-Induced Social and Synaptic Deficits in Neonatal Mice.Research (Washington, D.C.) · 2024Article
- The contributions of bacteria metabolites to the development of hepatic encephalopathy.Liver research (Beijing, China) · 2023Article
- Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Portosystemic shunt placement reveals blood signatures for the development of hepatic encephalopathy through mass spectrometry.Nature communications · 2023Article
- Connecting the Gut Microbiota and Neurodegenerative Diseases: the Role of Bile Acids.Molecular neurobiology · 2023Review
- Liver's influence on the brain through the action of bile acids.Frontiers in neuroscience · 2023Review
- The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Review
- Olive- and Coconut-Oil-Enriched Diets Decreased Secondary Bile Acids and Regulated Metabolic and Transcriptomic Markers of Brain Injury in the Frontal Cortexes of NAFLD Pigs.Brain sciences · 2022Article
- A critical review of bile acids and their receptors in hepatic encephalopathy.Analytical biochemistry · 2022Review
- A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction-Related Diseases.Oxidative medicine and cellular longevity · 2022Review
- Bile acid receptors and signaling crosstalk in the liver, gut and brain.Liver research (Beijing, China) · 2021Review
- Review
- 2021 ISHEN guidelines on animal models of hepatic encephalopathy.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Maintaining Digestive Health in Diabetes: The Role of the Gut Microbiome and the Challenge of Functional Foods.Microorganisms · 2021Review
- Farnesoid X Receptor Activation in Brain Alters Brown Adipose Tissue Function via the Sympathetic System.Frontiers in molecular neuroscience · 2021Article
- The Status of Bile Acids and Farnesoid X Receptor in Brain and Liver of Rats with Thioacetamide-Induced Acute Liver Failure.International journal of molecular sciences · 2020Article
- Neurodegeneration in juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease.American journal of physiology. Endocrinology and metabolism · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsHepatic encephalopathy is a serious neurologic complication of acute and chronic liver diseases. We previously showed that aberrant bile acid signaling contributes to the development of hepatic encephalopathy via farnesoid X receptor (FXR)-mediated mechanisms in neurons. In the brain, a novel alternative bile acid synthesis pathway, catalyzed by cytochrome p450 46A1 (Cyp46A1), is the primary mechanism by which the brain regulates cholesterol homeostasis. The aim of this study was to determine if FXR activation in the brain altered cholesterol homeostasis during hepatic encephalopathy.
methodsCyp7A1
resultsThere was an increase in membrane-bound and intracellular cholesterol in the cortex of mice treated with AOM that was associated with decreased Cyp46A1 expression. Strategies to inhibit FXR signaling prevented the down-regulation of Cyp46A1 and the accumulation of cholesterol. Treatment of mice with 2-hydroxypropyl-β-cyclodextrin attenuated the AOM-induced cholesterol accumulation in the brain and the cognitive and neuromuscular deficits without altering the underlying liver pathology.
conclusionsDuring hepatic encephalopathy, FXR signaling increases brain cholesterol and contributes to neurologic decline. Targeting cholesterol accumulation in the brain may be a possible therapeutic target for the management of hepatic encephalopathy.
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