ArticleCell metabolism2022
Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia.
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Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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103citing papers in PubMed
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103 citing papers in PubMed, 167 citations in OpenAlex.
- New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Integrative metabolomics and malonyl-proteomics reveal the crosstalk between metabolic reprogramming and lysine malonylation in liver fibrosis.Journal of physiology and biochemistry · 2026Article
- Bempedoic Acid: From Guidelines to the Real World.Journal of lipid and atherosclerosis · 2026Review
- Integrated multi-omics unravels solanesol's multi-organ protection mechanisms against insulin resistance in type 2 diabetic mice.Journal of advanced research · 2026Article
- Dyslipidaemia and hepatic steatosis: mechanisms and implications for lipid-lowering therapy.Nature reviews. Cardiology · 2026Review
- Plasma Metabolomic and Proteomic Profiling of the Mechanisms Underlying the Cumulative Impact of Co-occurring Psychiatric Disorders on Atopic Dermatitis.Acta dermato-venereologica · 2026Article
- Mutant p53-R280K hijacks SREBP1 to promote fatty acid synthesis and breast cancer progression via FASN.Molecular biology reports · 2026Article
- Perspectives on Bempedoic Acid, ATP-citrate lyase inhibitor: Targeting Lipid Metabolism and Inflammation.Journal of atherosclerosis and thrombosis · 2026Review
- Malonic acid promotes glycolytic activity in cumulus cells and improves the quality of bovine oocytes matured in vitro.The Journal of reproduction and development · 2026Article
- Multi-Omics Analysis Identifies Tryptophan Metabolism and Glycolysis as Potential Pathways Involved in the Protective Effects of Tormentic Acid Against Metabolic Associated Fatty Liver Disease.Pharmacology research & perspectives · 2026Article
- ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH.Nature communications · 2026Article
- The role of bempedoic acid in the management of dyslipidaemia in people with diabetes: an expert opinion of Italian diabetologists.Cardiovascular diabetology · 2026Review
- Lipid metabolism as a central driver of immune remodeling and therapeutic vulnerability in metastatic colorectal cancer.Lipids in health and disease · 2026Review
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- The GOLM1-ACLY pathway regulates macrophage-secreted EFEMP1 via H3K27ac modifications to drive tumor progression.Journal of advanced research · 2026Article
- Mitochondrial control of glycerolipid synthesis by a PEP shuttle.bioRxiv : the preprint server for biology · 2026Article
- ATP-citrate lyase is a critical regulator of physiological and pathological angiogenesis.Angiogenesis · 2026Article
- Hyperoside modulates bile acid and fatty acid metabolism, presenting a potentially promising treatment for non-alcoholic fatty liver disease.Journal of advanced research · 2026Article
- TSP50 attenuates metabolic dysfunction-associated steatotic liver disease via SCD1 degradation-mediated suppression of hepatocyte lipogenesis.Cellular & molecular biology letters · 2026Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 8 institutions in 3 countries.
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.
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.
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.
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.
Julie M LerouxCentre 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.
Pedrum Mohammadi-ShemiraniPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON L8L 2X2, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada.
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.
Zhichao WangDepartment of Molecular & Cellular Endocrinology, Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
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.
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.
Amir ReihaniDepartment of Medicine, Division of Respirology, McMaster University and St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
Brennan K SmithCentre 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.
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.
Tracy L NeroStructural Biology and Computational Design Laboratory, Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3065, Australia.
Michael W ParkerStructural Biology and Computational Design Laboratory, Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3065, Australia; ACRF Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
Kjetil AskDepartment of Medicine, Division of Respirology, McMaster University and St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
John W ScottProtein Chemistry & Metabolism, St. Vincent's Institute of Medical Research and School of Medicine, University of Melbourne, Fitzroy, VIC 3065, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia.
Lei JiangDepartment of Molecular & Cellular Endocrinology, Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA; Comprehensive Cancer Center, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Guillaume ParéPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON L8L 2X2, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada; Department of Medicine, Division of Respirology, McMaster University and St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON L8S 4L8, 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 L8S 4L8, Canada. Electronic address: gsteinberg@mcmaster.ca.
McMaster University Medical Centre · CAThe University of Melbourne · AUMcMaster University · CAPopulation Health Research Institute · CASt. Joseph’s Healthcare Hamilton · CACity of Hope · USCity Of Hope National Medical Center · USEsperion Therapeutics (United States) · US
Funding
CIHR 201709FDN-CEBA-116200
Abstract
Elevated liver de novo lipogenesis contributes to non-alcoholic steatohepatitis (NASH) and can be inhibited by targeting acetyl-CoA carboxylase (ACC). However, hypertriglyceridemia limits the use of pharmacological ACC inhibitors as a monotherapy. ATP-citrate lyase (ACLY) generates acetyl-CoA and oxaloacetate from citrate, but whether inhibition is effective for treating NASH is unknown. Here, we characterize a new mouse model that replicates many of the pathological and molecular drivers of NASH and find that genetically inhibiting ACLY in hepatocytes reduces liver malonyl-CoA, oxaloacetate, steatosis, and ballooning as well as blood glucose, triglycerides, and cholesterol. Pharmacological inhibition of ACLY mirrors genetic inhibition but has additional positive effects on hepatic stellate cells, liver inflammation, and fibrosis. Mendelian randomization of human variants that mimic reductions in ACLY also associate with lower circulating triglycerides and biomarkers of NASH. These data indicate that inhibiting liver ACLY may be an effective approach for treatment of NASH and dyslipidemia.
Indexed as
ATP Citrate (pro-S)-LyaseDyslipidemiasNon-alcoholic Fatty Liver DiseaseAcetyl-CoA CarboxylaseAnimalsLiverLiver CirrhosisMiceOxaloacetatesTriglyceridesAcetyl-CoA CarboxylaseATP Citrate (pro-S)-LyaseOxaloacetatesTriglyceridescardiovascular diseasediabetesfatty acid oxidationgluconeogenesishypertriglyceridemiainsulin resistancelipogenesisNASHnon-alcoholic steatohepatitissteatosis
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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.