ArticleNature communications2025
Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Pomegranate seed oil attenuates palmitic acid-induced hepatic injury through modulation of oxidative stress: insights from GC-Q-TOF-MS-based metabolomics.Journal of the science of food and agriculture · 2026Article
- Hexokinase-3 upregulation and histone H3K18 lactylation mediate murine liver fibrosis induced by Echinococcus multilocularis.PLoS neglected tropical diseases · 2026Article
- Design and evaluation of peroxiredoxin 1 agonist based on scaffold hopping of salvianolic acids and combinatorial click chemistry.Acta pharmacologica Sinica · 2026Article
- The Effect and Molecular Mechanism ofCurrent issues in molecular biology · 2026Article
- Spatiotemporal dynamics of reactive oxygen species: implications for cellular homeostasis and redox therapies.Cellular & molecular biology letters · 2026Review
- Moonlighting Functions of Mammalian Peroxiredoxins in Cellular Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Azoxystrobin induces mitochondrial dysfunction and mitochondrial pathway apoptosis by targeting the Prx1 Trp87 and Thr90 sites in oral leukoplakia.Frontiers in pharmacology · 2026Article
- Jiangtang Decoction for Type 2 Diabetes and NAFLD: Integrative AnalysisEndocrine, metabolic & immune disorders drug targets · 2026Article
- Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Pathogenesis and Treatment of Non-alcoholic Steatohepatitis and Its Fibrosis: A Systematic Review.Cureus · 2025Review
- A new perspective on iron-dependent cell death: PRDX-1-mediated ferroptosis in tumor cells.Apoptosis : an international journal on programmed cell death · 2025Review
- Mitochondrial dysfunction in the regulation of aging and aging-related diseases.Cell communication and signaling : CCS · 2025Review
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- Vitamin DFrontiers in nutrition · 2025Article
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Authors and funding
23 authors.
Funding
Abstract
Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice. Mechanistically, PRDX1 suppresses STAT signaling and protects mitochondrial function by scavenging hydrogen peroxide, and mitigating the oxidation of protein tyrosine phosphatases and lipid peroxidation. We further identify rosmarinic acid (RA) as a potent agonist of PRDX1. As revealed by the complex crystal structure, RA binds to PRDX1 and stabilizes its peroxidatic cysteine. RA alleviates NASH through specifically activating PRDX1's peroxidase activity. Thus, beyond revealing the molecular mechanism underlying PA promoting oxidative stress and NASH, our study suggests that boosting PRDX1's peroxidase activity is a promising intervention for treating NASH.
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