ArticleClinical and molecular hepatology2025
Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation.
Article in Clinical and molecular hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed.
- Prime editing models the MTARC1 A165T variant in human liver organoids, demonstrating reduced steatosis, inflammation, and fibrosis.Hepatology communications · 2026Article
- Circadian Disruption Is Associated with Elevated Whole-Semen mtDNA Copy Number and ImplicatesInternational journal of molecular sciences · 2026Article
- Correspondence to editorial 2 on "Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A".Clinical and molecular hepatology · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Opportunities and challenges in controlling metabolic dysfunction-associated steatotic liver disease: Editorial on "Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation".Clinical and molecular hepatology · 2026Article
- MTARC1 p.A165 ablation reduces hepatocellular carcinoma aggressiveness in vitro and in vivo.Clinical and molecular hepatology · 2026Article
- Correspondence to editorial on "Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation".Clinical and molecular hepatology · 2026Article
- Metabolic dysfunction-associated steatotic liver disease: On track to become the dominant etiology of hepatocellular carcinoma: Reply to correspondence on "Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-oxidation".Clinical and molecular hepatology · 2026Article
- Loss of Mtarc1 Protects Against Steatotic Liver Disease in Mice.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Article
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- The Hepatoprotective Properties of Gentiopicroside, Sweroside, and Swertiamarin Against Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Biomolecules · 2025Article
- Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization.International journal of molecular sciences · 2025Article
Corrections and comments
- Commented on by
Authors and funding
18 authors.
Funding
Abstract
BACKGROUND/
aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic. The disease has a strong genetic component, and a common missense variant (rs2642438) in the mitochondrial amidoxime-reducing component 1 (MARC1) gene confers protection against its onset and severity. However, there are contrasting results regarding the mechanisms that promote this protection.
methodsWe downregulated MARC1 in primary human hepatocytes (PHHs) using short interfering RNA (siRNA). We measured neutral lipid content by Oil-Red O staining and fatty acid oxidation by radiolabeled tracers. We also performed RNA-sequencing and proteomic analysis using LC-MS. Additionally, we analyzed data from 239,075 participants from the UK Biobank.
resultsDownregulation of MARC1 reduced neutral lipid content in PHHs homozygous for the wild type (p.A165, risk), but not for the mutant (p.T165, protective), allele. We found that this reduction was mediated by increased fatty acid utilization via β-oxidation. Consistent with these results, we found that the levels of 3-hydroxybutyrate, a by-product of β-oxidation, were higher in carriers of the rs2642438 minor allele among samples from the UK biobank, indicating higher β-oxidation in these individuals. Moreover, downregulation of the MARC1 p.A165 variant resulted in a more favorable phenotype by reducing ferroptosis and reactive oxygen species levels.
conclusionMARC1 downregulation in carriers of the risk allele results in lower hepatocyte neutral lipids content due to higher β-oxidation, while upregulating beneficial pathways involved in cell survival.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.