Evidence map›Paper›PMID 37729871›Full record

ArticleCell reports. Medicine2023

Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice.

Eric M Desjardins, Jianhan Wu, Declan C T Lavoie, Elham Ahmadi, Logan K Townsend, Marisa R Morrow, Dongdong Wang, Evangelia E Tsakiridis, Battsetseg Batchuluun, Russta Fayyazi and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
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

22 citing papers in PubMed, 25 citations in OpenAlex.

  1. New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026
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  10. Molecular targets of bempedoic acid and related decoy fatty acids.Trends in endocrinology and metabolism: TEM · 2025
    Review
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  12. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Targeting Metabolism: Innovative Therapies for MASLD Unveiled.International journal of molecular sciences · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Eric M DesjardinsCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Jianhan WuCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Population Health Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
Declan C T LavoieCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Elham AhmadiCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Logan K TownsendCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Marisa R MorrowCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Dongdong WangCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Evangelia E TsakiridisCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Battsetseg BatchuluunCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Russta FayyaziCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Jacek M KwiecienDepartment of Pathology, McMaster University, Hamilton, ON L8S 4L8, Canada.
Theodoros TsakiridisCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Department of Oncology, McMaster University, Hamilton, ON L8S 4L8, Canada.
James S V LallyCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Guillaume ParéCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Population Health Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
Stephen L PinkoskyEsperion Therapeutics, Inc., Ann Arbor, MI, USA.
Gregory R SteinbergCentre for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton ON L8S 4L8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8L 2X2, Canada. Electronic address: gsteinberg@mcmaster.ca.
McMaster University · CAEsperion Therapeutics (United States) · USPopulation Health Research Institute · CA

Funding

CIHR 201709FDN-CEBA-116200
6 · The paper itself

Abstract

Increased liver de novo lipogenesis (DNL) is a hallmark of nonalcoholic steatohepatitis (NASH). A key enzyme controlling DNL upregulated in NASH is ATP citrate lyase (ACLY). In mice, inhibition of ACLY reduces liver steatosis, ballooning, and fibrosis and inhibits activation of hepatic stellate cells. Glucagon-like peptide-1 receptor (GLP-1R) agonists lower body mass, insulin resistance, and steatosis without improving fibrosis. Here, we find that combining an inhibitor of liver ACLY, bempedoic acid, and the GLP-1R agonist liraglutide reduces liver steatosis, hepatocellular ballooning, and hepatic fibrosis in a mouse model of NASH. Liver RNA analyses revealed additive downregulation of pathways that are predictive of NASH resolution, reductions in the expression of prognostically significant genes compared with clinical NASH samples, and a predicted gene signature profile that supports fibrosis resolution. These findings support further investigation of this combinatorial therapy to treat obesity, insulin resistance, hypercholesterolemia, steatohepatitis, and fibrosis in people with NASH.

Indexed as

Insulin ResistanceNon-alcoholic Fatty Liver DiseaseAcyltransferasesAnimalsHumansLiver CirrhosisMiceAcyltransferasesACLYbempedoic acidcombination treatmentfatty acid metabolismGLP-1R agonisthepatic fibrosislipogenesisliraglutideMASHmouse modelNAFLDNASHsemaglutide

Identifiers

PMID37729871
PMCPMC10518624
OpenAlexW4386865750

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.