ArticleDevelopment (Cambridge, England)2009
TNFalpha-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish S-adenosylhomocysteine hydrolase.
Article in Development (Cambridge, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
53 citing papers in PubMed, 88 citations in OpenAlex.
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- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Mitochondrial protein Mrpl13 regulates zebrafish liver development through the mTORC1-mitochondrial homeostasis pathway.Communications biology · 2026Article
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- Fatty Liver in Fish: Metabolic Drivers, Molecular Pathways and Physiological Solutions.Animals : an open access journal from MDPI · 2026Review
- Effect of gentiopicroside on endogenous formaldehyde homocysteine-pathway related proteins in rats with non-alcoholic steatohepatitis.Frontiers in pharmacology · 2025Article
- Optimized methods to image hepatic lipid droplets in zebrafish larvae.Disease models & mechanisms · 2024Article
- Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine.Biomedicines · 2024Review
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- Non-Alcoholic Fatty Liver Disease: Translating Disease Mechanisms into Therapeutics Using Animal Models.International journal of molecular sciences · 2023Review
- Functional and Pathological Roles of AHCY.Frontiers in cell and developmental biology · 2021Review
- Zebrafish for Personalized Regenerative Medicine; A More Predictive Humanized Model of Endocrine Disease.Frontiers in endocrinology · 2020Review
- Lipid Modulating Anti-oxidant Stress Activity of Gastrodin on Nonalcoholic Fatty Liver Disease Larval Zebrafish Model.International journal of molecular sciences · 2019Article
- Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish.Journal of hepatology · 2019Article
- Metabolite and gene expression profiles suggest a putative mechanism through which high dietary carbohydrates reduce the content of hepatic betaine in Megalobrama amblycephala.Metabolomics : Official journal of the Metabolomic Society · 2018Article
- Blocking fatty acid-fueled mROS production within macrophages alleviates acute gouty inflammation.The Journal of clinical investigation · 2018Article
- Homocysteine regulates fatty acid and lipid metabolism in yeast.The Journal of biological chemistry · 2018Article
- Epigenetically mediated inhibition of S-adenosylhomocysteine hydrolase and the associated dysregulation of 1-carbon metabolism in nonalcoholic steatohepatitis and hepatocellular carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Deregulation of methionine metabolism as determinant of progression and prognosis of hepatocellular carcinoma.Translational gastroenterology and hepatology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor S-adenosylmethionine (SAM). Elevated SAH in dtp larvae was associated with mitochondrial defects and increased expression of tnfa and pparg, an ortholog of the mammalian lipogenic gene. Antisense knockdown of tnfa rescued hepatic steatosis and liver degeneration in dtp larvae, whereas the overexpression of tnfa and the hepatic phenotype were unchanged in dtp larvae reared under germ-free conditions. These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFalpha. Although heterozygous dtp larvae had no discernible phenotype, hepatic steatosis was present in heterozygous adult dtp fish and in wild-type adult fish treated with an Ahcy inhibitor. These data argue that AHCY polymorphisms and AHCY inhibitors, which have shown promise in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection. Supporting this idea, hepatic injury and steatosis have been noted in patients with recently discovered AHCY mutations.
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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.