The vital role of ATP citrate lyase in chronic diseases

J Mol Med (Berl). 2020 Jan;98(1):71-95. doi: 10.1007/s00109-019-01863-0. Epub 2019 Dec 19.


Chronic or non-communicable diseases are the leading cause of death worldwide; they usually result in long-term illnesses and demand long-term care. Despite advances in molecular therapeutics, specific biomarkers and targets for the treatment of these diseases are required. The dysregulation of de novo lipogenesis has been found to play an essential role in cell metabolism and is associated with the development and progression of many chronic diseases; this confirms the link between obesity and various chronic diseases. The main enzyme in this pathway-ATP-citrate lyase (ACLY), a lipogenic enzyme-catalyzes the critical reaction linking cellular glucose catabolism and lipogenesis. Increasing lines of evidence suggest that the modulation of ACLY expression correlates with the development and progressions of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases, diabetes, obesity, inflammation, and cancer. Recent studies suggest that the inhibition of ACLY activity modulates the glycolysis and lipogenesis processes and stimulates normal physiological functions. This comprehensive review aimed to critically evaluate the role of ACLY in the development and progression of different diseases and the effects of its downregulation in the prevention and treatment of these diseases.

Keywords: ATP citrate lyase; Chronic diseases; Fatty acid biosynthesis; Lipogenic enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Citrate (pro-S)-Lyase / antagonists & inhibitors*
  • ATP Citrate (pro-S)-Lyase / metabolism*
  • Aged
  • Aged, 80 and over
  • Animals
  • Chronic Disease
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology*
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Male
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Noncommunicable Diseases* / drug therapy
  • Obesity / drug therapy
  • Obesity / enzymology*


  • Enzyme Inhibitors
  • ATP Citrate (pro-S)-Lyase