ArticleCell metabolism2025
Bempedoic acid suppresses diet-induced hepatic steatosis independently of ATP-citrate lyase.
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Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
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Who cites it
20 citing papers in PubMed.
- Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.Science advances · 2026Article
- Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Perspectives on Bempedoic Acid, ATP-citrate lyase inhibitor: Targeting Lipid Metabolism and Inflammation.Journal of atherosclerosis and thrombosis · 2026Review
- ACLY-Driven Metabolic Reprogramming Promotes Histone Acetylation and Inflammation-Associated Fibrosis in Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of bempedoic acid in the management of dyslipidaemia in people with diabetes: an expert opinion of Italian diabetologists.Cardiovascular diabetology · 2026Review
- A Triterpenoid-Enriched GLE70 Fraction FromFood science & nutrition · 2026Article
- Simultaneous Inhibition of ACLY and OGDH Has a Synergistic Effect on Hepatocellular Carcinoma Cell Lines.bioRxiv : the preprint server for biology · 2026Article
- Nutrient-driven histone acetylation underlies energy storage and mobilization.Molecular metabolism · 2026Article
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- UBQLN1 Inhibition reduces MASH progression through downregulating SIKE/p38 MAPK pathway in hepatocyte.Journal of nanobiotechnology · 2026Article
- ACLY Safeguards Copper Homeostasis to Sustain Brown Adipose Tissue Thermogenesis and Restrain Diet-Induced Obesity.Research (Washington, D.C.) · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Molecular targets of bempedoic acid and related decoy fatty acids.Trends in endocrinology and metabolism: TEM · 2025Review
- The pathogenesis of hepatic steatosis in MASLD: a lipid droplet perspective.The Journal of clinical investigation · 2025Article
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- The impact of metabolic dysfunction-associated steatotic liver disease (MASH) on the high risk of cardiovascular disease in CKD: interconnections and management.Clinical kidney journal · 2025Review
- The Connection Between Lipid Metabolism in the Heart and Liver of Wuzhishan Pigs.Biomolecules · 2025Article
- Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis.Cell reports · 2025Article
- Advancing de novo lipogenesis: Genetic and metabolic insights.Cell metabolism · 2025Article
- Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment.Frontiers in immunology · 2025Review
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Authors and funding
22 authors.
Joyce Y LiuDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ramya S KunaDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Laura V PinheiroDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Phuong T T NguyenDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jaclyn E WellesDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jack M DrummondDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nivitha MuraliDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Prateek V SharmaDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Julianna G SuppleeDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mia ShiueDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Steven ZhaoDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aimee T FarriaDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Avi KumarDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Mauren L RuchhoeftDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Christina DemetriadouDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Aging + Cardiovascular Discovery Center, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Daniel S KantnerAging + Cardiovascular Discovery Center, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Adam ChatoffAging + Cardiovascular Discovery Center, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Emily MegillAging + Cardiovascular Discovery Center, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Paul M TitchenellDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nathaniel W SnyderAging + Cardiovascular Discovery Center, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Christian M MetalloDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: metallo@salk.edu.
Kathryn E WellenDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: wellenk@upenn.edu.
Funding
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3MUniversity of Pennsylvania Postdoctoral Opportunities in Research and TeachingK12GM081259 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Janis K. Burkhardt · 2007 to 2026
$20.1MDiabetes, Endocrine, and MetabolismT32DK007314 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DORIS A STOFFERS, Patrick Seale · 1986 to 2026
$9.0MPREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008216 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 1987 to 2023
$8.3MTraining In Tumor VirologyT32CA115299 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2021
$4.7MMetabolic regulation and inhibition of ATP-citrate lyaseR01CA262055 · NCI · UNIVERSITY OF PENNSYLVANIA · PI George Burslem, Ronen Marmorstein · 2022 to 2026
$3.2MMetabolic and epigenetic reprogramming in cyclin E high ovarian cancerR01CA259111 · NCI · WISTAR INSTITUTE · PI AIRD, KATHERINE MARIE, SNYDER, NATHANIEL W. · 2021 to 2025
$2.9MAcetyl-CoA metabolism and nutrient sensing in adipocytesR01DK116005 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GUERTIN, DAVID A, WELLEN, KATHRYN ELAINE · 2019 to 2022
$2.0MNon-essential amino acids and sphingolipid diversity in cancer progressionR01CA234245 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI METALLO, CHRISTIAN MICHAEL · 2019 to 2023
$1.9MDefining an acetyl-CoA sensing mechanism as a form of inter-organelle communication in cancerR01CA228339 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WELLEN, KATHRYN ELAINE · 2018 to 2022
$1.9MQuantification of compartmentalized metabolism in eukaryotic systemsR01GM132261 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI SNYDER, NATHANIEL W. · 2019 to 2023
$1.8MHepatic mTORC1 Signaling and the Regulation of Lipid HomeostasisR01DK125497 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI TITCHENELL, PAUL MICHAEL · 2021 to 2024
$1.7MNCI NIH HHS F31 CA260781NCI NIH HHS F99 CA222741NCI NIH HHS R01 CA228339NCI NIH HHS R01 CA234245NCI NIH HHS R01 CA259111NCI NIH HHS R01 CA262055NCI NIH HHS T32 CA115299NIDDK NIH HHS F30 DK126353NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK116005NIDDK NIH HHS R01 DK125497NIDDK NIH HHS R01 DK138011NIDDK NIH HHS R56 DK116005NIDDK NIH HHS T32 DK007314NIGMS NIH HHS K12 GM081259NIGMS NIH HHS R01 GM132261NIGMS NIH HHS T32 GM008216NIGMS NIH HHS T32 GM142606
Abstract
ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in metabolic dysfunction-associated steatotic liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol-lowering drug bempedoic acid (BPA), which also improves steatosis in mice. While BPA potently suppresses hepatic DNL and increases fat catabolism, it is unclear if ACLY is its primary molecular target in reducing liver triglyceride. We show that on a Western diet, loss of hepatic ACLY alone or together with the acetyl-CoA synthetase ACSS2 unexpectedly exacerbates steatosis, linked to reduced PPARα target gene expression and fatty acid oxidation. Importantly, BPA treatment ameliorates Western diet-mediated triacylglyceride accumulation in both WT and liver ACLY knockout mice, indicating that its primary effects on hepatic steatosis are ACLY independent. Together, these data indicate that hepatic ACLY plays an unexpected role in restraining diet-dependent lipid accumulation and that BPA exerts substantial effects on hepatic lipid metabolism independently of ACLY.
Indexed as
ATP Citrate (pro-S)-LyaseDicarboxylic AcidsFatty AcidsFatty LiverLiverMice, Inbred C57BLMice, KnockoutAcetate-CoA LigaseAnimalsCoenzyme A LigasesDiet, WesternLipid MetabolismLipogenesisMaleMicePPAR alpha8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acidAcetate-CoA LigaseACSS2 protein, mouseATP Citrate (pro-S)-LyaseCoenzyme A LigasesDicarboxylic AcidsFatty AcidsPPAR alphaTriglyceridesACLYACSS2bempedoic acidlipid metabolismmetabolic dysfunction-associated steatotic liver diseasePPARα
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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 Socratic graph.