Academic Journal
Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).
| Τίτλος: | Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review). |
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| Συγγραφείς: | Zhu B; Department of Ultrasound, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Wang C; Department of Interventional Radiology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Liu P; Department of Endocrinology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Qu Z; Department of Radiation Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Qi R; Department of Gastroenterology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Chen S; Department of Ultrasound, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China., Niu H; Department of Interventional Radiology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China. |
| Πηγή: | International journal of molecular medicine [Int J Mol Med] 2026 Aug; Vol. 58 (2). Date of Electronic Publication: 2026 Jun 11. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: D.A. Spandidos Country of Publication: Greece NLM ID: 9810955 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-244X (Electronic) Linking ISSN: 11073756 NLM ISO Abbreviation: Int J Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Athens, Greece : D.A. Spandidos, [1998- |
| Ιατρικοί όροι (MeSH): | Arginine*/metabolism , Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/pathology , Urea*/metabolism, Nitric Oxide/metabolism ; Humans ; Animals ; Signal Transduction |
| Περίληψη: | Non‑alcoholic fatty liver disease (NAFLD) and its advanced form, non‑alcoholic steatohepatitis (NASH), are now leading causes of chronic liver disease worldwide. Recent evidence highlights the central role of urea cycle and arginine metabolism dysregulation in NAFLD/NASH pathogenesis. Downregulation of key urea cycle enzymes, such as carbamoyl phosphate synthetase 1, ornithine transcarbamylase and argininosuccinate synthase, impairs ammonia detoxification, leading to hyperammonemia, mitochondrial dysfunction and oxidative stress. Epigenetic modifications, notably DNA methylation and histone changes, contribute to this metabolic reprogramming. Aberrant arginine metabolism, particularly the imbalance between urea and nitric oxide (NO) pathways, exacerbates liver inflammation and fibrosis through increased inducible nitric oxide synthase (NOS) activity in macrophages and hepatic stellate cells, driving excessive NO and polyamine production. In contrast, physiological NO signaling via endothelial NOS supports mitochondrial health and metabolic homeostasis. Clinically, urea cycle and arginine metabolites, including blood ammonia and urea cycle metabolites, serve as potential biomarkers for disease severity. Restoring urea cycle function and rebalancing arginine‑NO metabolism through targeted interventions, such as citrulline/arginine supplementation or enzyme modulation, are promising strategies. |
| Contributed Indexing: | Keywords: non‑alcoholic fatty liver disease; non‑alcoholic steatohepatitis; urea cycle |
| Substance Nomenclature: | 94ZLA3W45F (Arginine) 8W8T17847W (Urea) 31C4KY9ESH (Nitric Oxide) |
| Entry Date(s): | Date Created: 20260611 Date Completed: 20260614 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13252948 |
| DOI: | 10.3892/ijmm.2026.5886 |
| PMID: | 42272250 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1791-244X |
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| DOI: | 10.3892/ijmm.2026.5886 |