ArticleMetabolism: clinical and experimental2024
Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.
Article in Metabolism: clinical and experimental, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation.Gut microbes · 2026Review
- In vitro approaches for modelling gut-liver crosstalk in drug-induced liver injury.Archives of toxicology · 2026Review
- mJournal of cardiothoracic surgery · 2026Article
- Sexually dimorphic ATF4 expression in the fat confers female stress tolerance in Drosophila melanogaster.Genetics · 2026Article
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- Lianhe Xiaozhi ointment ameliorates metabolic dysfunction-associated steatotic liver diseaseWorld journal of gastroenterology · 2026Article
- Low-dose galactose rebalances HBP-mTORC1-SREBP-1c signaling to suppress hepatic lipogenesis and protect against early-stage alcohol-related liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- The predictive role of ammonia in liver-related decompensation and mortality in patients with compensated cirrhosis: A retrospective cohort study.Canadian liver journal · 2026Article
- Reference Gene Validation for Quantitative PCR Analysis in 2D and 3D AML12 Hepatocyte Models.Biomedicines · 2026Article
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Dietary patterns influencing the human colonic microbiota from infancy to centenarian age: a narrative review.Frontiers in nutrition · 2025Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsDysbiosis contributes to alcohol-associated liver disease (ALD); however, the precise mechanisms remain elusive. Given the critical role of the gut microbiota in ammonia production, we herein aim to investigate whether and how gut-derived ammonia contributes to ALD.
methodsBlood samples were collected from human subjects with/without alcohol drinking. Mice were exposed to the Lieber-DeCarli isocaloric control or ethanol-containing diets with and without rifaximin (a nonabsorbable antibiotic clinically used for lowering gut ammonia production) supplementation for five weeks. Both in vitro (NH
resultsChronic alcohol consumption causes hyperammonemia in both mice and human subjects. In healthy livers and hepatocytes, ammonia exposure upregulates the expression of urea cycle genes, elevates hepatic de novo lipogenesis (DNL), and increases fat accumulation. Intriguingly, ammonia promotes ethanol catabolism and acetyl-CoA formation, which, together with ammonia, synergistically facilitates intracellular fat accumulation in hepatocytes. Mechanistic investigations uncovered that ATF4 activation, as a result of ER stress induction and general control nonderepressible 2 activation, plays a central role in ammonia-provoked DNL elevation. Rifaximin ameliorates ALD pathologies in mice, concomitant with blunted hepatic ER stress induction, ATF4 activation, and DNL activation.
conclusionsAn overproduction of ammonia by gut microbiota, synergistically interacting with ethanol, is a significant contributor to ALD pathologies.
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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.