HYPERLIPIDEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. DurringtonApolipoprotein F: a natural inhibitor of cholesteryl ester transfer protein and a key regulator of lipoprotein metabolismLiu, Yan; Morton, Richard E.Author Information Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Correspondence to Richard E. Morton, Department of Cardiovascular and Metabolic Sciences, NC10, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA. Tel: +1 216 444 5850; e-mail: email@example.com Current Opinion in Lipidology: August 2020 - Volume 31 - Issue 4 - p 194-199 doi: 10.1097/MOL.0000000000000688 Buy Metrics Abstract Purpose of review The aim of this study is to highlight recent studies that have advanced our understanding of apolipoprotein F (ApoF) and its role in lipid metabolism. Recent findings Previous studies showed that ApoF hepatic mRNA levels are suppressed by fat-enriched diets. Recent studies show this downregulation is mediated by agonist-induced binding of liver X receptor (LXR) and PPARalpha to a regulatory element in the ApoF promoter. First-of-kind in-vivo studies show ApoF lowers low-density lipoprotein levels and enhances reverse cholesterol transport in fat-fed hamsters. Summary Diverse studies collectively provide compelling evidence that cholesteryl ester transfer protein (CETP) plays an important role in regulating lipid metabolism. Inhibiting CETP raises HDL cholesterol. However, considering the recent failures of pharmacological inhibitors of CETP in clinical trials, it does not seem likely that global inhibition of CETP will be beneficial. ApoF is a minor apolipoprotein that functions as a natural inhibitor of CETP. However, ApoF is not a general inhibitor of CETP, but rather it preferentially inhibits CETP activity with LDL. Therefore, ApoF tailors CETP activity so that less tissue-derived cholesterol traffics from HDL into the LDL compartment. Lower LDL cholesterol levels have recognized clinical benefit for reduced cardiovascular disease. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.