ArticleNature metabolism2023
Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- Itaconate as the endogenous brake of proinflammatory macrophage activation alleviates inflammation in liver fibrogenesis.Hepatology communications · 2026Article
- 4-Octyl Itaconate Attenuates Age-Induced Parotid Gland Dysfunction Through the Suppression of Fibrosis and Lipid Deposition by AMPKα/PPARα and the Inhibition of Oxidative Stress via the AMPKα/Nrf2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Macrophage-derived itaconate is a negative regulator of adipose tissue thermogenesis.Nature metabolism · 2026Article
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Virgin Coconut Oil Attenuates Diabetic Kidney Disease via Gut Microbiota-Metabolism-Inflammation Axis Modulation in Type 2 Diabetic Mice.Food science & nutrition · 2026Article
- Role of itaconate in intestinal disease (Review).International journal of molecular medicine · 2026Review
- Human pneumovirus induces IFN-dependent expression of the immune-responsive gene 1 and is inhibited by 4-octyl itaconate in human macrophages.NAR molecular medicine · 2026Article
- Sex-based multiomics analysis uncovers metabolic and molecular mediators linking MASH and atherosclerosis.JHEP reports : innovation in hepatology · 2026Article
- Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity.Biomolecules · 2026Review
- Revisiting macrophage metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: mechanisms, regulation, and therapeutic breakthroughs.Frontiers in immunology · 2026Review
- Effects of enzyme preparations on growth performance, meat quality, and hepatic transcriptome of yaks.Frontiers in veterinary science · 2026Article
- Bioinformatics and machine learning approaches to explore the biomarkers in fatty acid degradation linked to osteoarthritis.Frontiers in immunology · 2026Article
- Airway immunometabolic responses during pulmonary bacterial and viral infections.Cell reports · 2025Review
- Itaconic Acid Activates Lysosomal Biogenesis and Autophagy Flux and Mitigates High-Fat Diet-Induced Liver Lipid Accumulation in Largemouth Bass (Antioxidants (Basel, Switzerland) · 2025Article
- Spectroscopic method for measuring activity of cis-aconitate decarboxylase, an important metabolic regulator of immune responses.Analytical biochemistry · 2025Article
- Protective Effect of Mesaconate on Autoimmune Hepatitis via Suppression of Inflammatory Response and Oxidative Stress.Journal of clinical and translational hepatology · 2025Article
- Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance.Cell metabolism · 2025Article
- A carbon trail to follow: unveiling itaconate's metabolism in vivo.Immunometabolism (Cobham, Surrey) · 2025Article
- ORMDL2 Promotes the Growth of Glioma through mTORC1-Mediated Fatty Acid Metabolism.Applied biochemistry and biotechnology · 2025Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Itaconate, the product of the decarboxylation of cis-aconitate, regulates numerous biological processes. We and others have revealed itaconate as a regulator of fatty acid β-oxidation, generation of mitochondrial reactive oxygen species and the metabolic interplay between resident macrophages and tumors. In the present study, we show that itaconic acid is upregulated in human non-alcoholic steatohepatitis and a mouse model of non-alcoholic fatty liver disease. Male mice deficient in the gene responsible for itaconate production (immunoresponsive gene (Irg)-1) have exacerbated lipid accumulation in the liver, glucose and insulin intolerance and mesenteric fat deposition. Treatment of mice with the itaconate derivative, 4-octyl itaconate, reverses dyslipidemia associated with high-fat diet feeding. Mechanistically, itaconate treatment of primary hepatocytes reduces lipid accumulation and increases their oxidative phosphorylation in a manner dependent upon fatty acid oxidation. We propose a model whereby macrophage-derived itaconate acts in trans upon hepatocytes to modulate the liver's ability to metabolize fatty acids.
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