Journal
TRENDS IN MOLECULAR MEDICINE
Volume 23, Issue 11, Pages 1047-1063Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2017.09.001
Keywords
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Funding
- Canada Research Chair in Metabolism and Obesity
- J. Bruce Duncan Endowed Chair in Metabolic Diseases at McMaster University
- Canadian Institutes of Health Researchand Diabetes Canada
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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.
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