Targeting ATP-Citrate Lyase in Hyperlipidemia and Metabolic Disorders

Trends Mol Med. 2017 Nov;23(11):1047-1063. doi: 10.1016/j.molmed.2017.09.001. Epub 2017 Oct 6.


Chronic overnutrition and a sedentary lifestyle promote imbalances in metabolism, often manifesting as risk factors for life-threating diseases such as atherosclerotic cardiovascular disease (ASCVD) and nonalcoholic fatty liver disease (NAFLD). Nucleocytosolic acetyl-coenzyme A (CoA) has emerged as a central signaling node used to coordinate metabolic adaptations in response to a changing nutritional status. ATP-citrate lyase (ACL) is the enzyme primarily responsible for the production of extramitochondrial acetyl-CoA and is thus strategically positioned at the intersection of nutrient catabolism and lipid biosynthesis. Here, we discuss recent findings from preclinical studies, as well as Mendelian and clinical randomized trials, demonstrating the importance of ACL activity in metabolism, and supporting its inhibition as a potential therapeutic approach to treating ASCVD, NAFLD, and other metabolic disorders.

Publication types

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

MeSH terms

  • ATP Citrate (pro-S)-Lyase / metabolism*
  • Acetyl Coenzyme A / metabolism
  • Animals
  • Humans
  • Hyperlipidemias / metabolism*
  • Metabolic Diseases / metabolism*
  • Randomized Controlled Trials as Topic


  • Acetyl Coenzyme A
  • ATP Citrate (pro-S)-Lyase

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