Related Experiment Video

Updated: Mar 9, 2026

Click-Chemistry Based Fluorometric Assay for Apolipoprotein N-acyltransferase from Enzyme Characterization to High-Throughput Screening
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Click-Chemistry Based Fluorometric Assay for Apolipoprotein N-acyltransferase from Enzyme Characterization to High-Throughput Screening

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ATP-citrate lyase: genetics, molecular biology and therapeutic target for dyslipidemia

Amy C Burke1, Murray W Huff

  • 1aDepartment of Biochemistry bDepartment of Medicine cRobarts Research Institute, The University of Western Ontario, London, Ontario, Canada.

Current Opinion in Lipidology
|January 7, 2017
PubMed
Abstract

Insights

ATP-citrate lyase (ACLY) inhibition effectively lowers LDL cholesterol. Bempedoic acid, an ACLY inhibitor, shows promise for cardiovascular medicine, with ongoing trials to confirm its long-term benefits.

Area of Science:

  • Biochemistry
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • ATP-citrate lyase (ACLY) is a key enzyme in lipogenesis, linking glucose metabolism to cholesterol and fatty acid synthesis.
  • Genetic variations in ACLY influence cancer growth and lipid metabolism.
  • ACLY deficiency in mice demonstrates protective effects against hepatic steatosis and dyslipidemia.

Purpose of the Study:

  • To review ATP-citrate lyase (ACLY) as a therapeutic target for lowering LDL cholesterol (LDL-C).
  • To explore the genetics, molecular biology, and inhibition strategies for ACLY.
  • To assess the role of ACLY in lipid metabolism and cardiovascular health.

Main Methods:

  • Review of existing literature on ACLY's role in human health and disease.
  • Analysis of genetic studies linking ACLY variants to disease phenotypes.
  • Evaluation of preclinical data for ACLY inhibitors, including bempedoic acid.
  • Summary of clinical trial results for bempedoic acid in hypercholesterolemic patients.

Main Results:

  • ACLY inhibition provides a novel strategy for lowering LDL-C.
  • Bempedoic acid, a potent ACLY inhibitor, reduces dyslipidemia and atherosclerosis in animal models.
  • Phase 2 clinical trials demonstrate bempedoic acid's efficacy in lowering LDL-C, alone or in combination therapy, including in statin-intolerant patients.

Conclusions:

  • The efficacy of bempedoic acid validates ACLY inhibition as a therapeutic approach for managing hypercholesterolemia.
  • Further Phase 3 studies and long-term cardiovascular outcome trials are necessary to establish ACLY as a significant target in cardiovascular medicine.

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