Evidence map›Paper›PMID 41527487›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2026

Loss of Mtarc1 Protects Against Steatotic Liver Disease in Mice.

Xiaofei Yin, Caroline Bickerton, Bryan MacDonald, Alessandro Arduini, Yunlong Shi, Mary Haas, Amy Deik, Mark Chaffin, Erika Kovacs-Bogdan, Julian Avila Pacheco and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Xiaofei YinCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Caroline BickertonCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Bryan MacDonaldCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0002-2090-2066
Alessandro ArduiniCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Yunlong ShiBayer U.S. LLC, Cambridge, Massachusetts, USA.
Mary HaasCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Amy DeikMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Mark ChaffinCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Erika Kovacs-BogdanCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Julian Avila PachecoMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Maiwen AmegadjieCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Bidur BhandaryCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Shayan SadreCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Thomas RathjenBayer AG, Pharmaceutical Division, Berlin, Germany.
Irinna PapangeliBayer U.S. LLC, Cambridge, Massachusetts, USA.
Raymond T ChungGI Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Russell GoodmanGI Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Melina ClaussnitzerCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Clary ClishMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Alexander EhrmannBayer AG, Pharmaceutical Division, Wuppertal, Germany.
Alison LeedCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0001-5972-1548
Patrick T EllinorCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Funding

IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
Using Electrocardiogram Genetics to Inform Arrhythmia RiskR01HL157635 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS, MIRSHAHI, TOORAJ · 2022 to 2025
$2.9M
American Heart Association 18SFRN34110082American Heart Association 961045American Heart Association-American Stroke Association 961045 - PATRICK ELLINORBayer AGEuropean Union MAESTRIA 965286NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL157635
6 · The paper itself

Abstract

BACKGROUND &

aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) spans from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and can progress to cirrhosis or hepatocellular carcinoma. Despite its prevalence, effective therapies are lacking. Recent genome-wide association studies identified a common missense variant (rs2642438) in the Mitochondrial Amidoxime Reducing Component 1 (MTARC1) gene that protects against liver cirrhosis without increasing cardiovascular disease risk. Biochemical and disease risk signatures associated with carriers of this missense variant also aligned with those of a known loss-of-function MTARC1 variant, suggesting mARC1 inhibition as a potential MASLD treatment.

methodsTo validate mARC1 loss-of-function as protective against MASLD, we generated Mtarc1 knockout (KO) mice and placed them on a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Effects of Mtarc1 KO on obesity and type 2 diabetes were explored using a high-fat diet. Hepatocytes from Mtarc1 KO mice were isolated to explore the molecular mechanisms by which Mtarc1 KO impacts lipid metabolism.

resultsMtarc1 KO mice exhibited no vital growth or development defects. With a high-fat diet-induced obesity model, obese Mtarc1 KO mice exhibited reduced liver mass and lower cholesterol levels, with no effect on glucose homeostasis. In a CDAHFD-induced MASLD model, mARC1 deficiency significantly reduced liver steatosis, profibrosis, and inflammation. Untargeted metabolomics profiling further showed hepatic enrichment of phospholipids in Mtarc1 KO mice. Primary hepatocytes isolated from Mtarc1 KO mice exhibited reduced lipid droplet accumulation, decreased fatty acid uptake, and increased lipid secretion.

conclusionsThese findings support mARC1 inhibition as a promising therapeutic strategy for MASLD/MASH.

Indexed as

Fatty LiverNon-alcoholic Fatty Liver DiseaseAmidohydrolasesAnimalsCholine DeficiencyDiet, High-FatDisease Models, AnimalGPI-Linked ProteinsHepatocytesLipid MetabolismLiverMaleMiceMice, Inbred C57BLMice, KnockoutObesityAmidohydrolasesGPI-Linked Proteinspantetheinasemetabolic dysfunction‐associated steatotic liver diseaseMtarc1phospholipidprofibrosissteatosis

Identifiers

PMID41527487
PMCPMC13552137

What OpenQuestion holds

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Registered trials

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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.