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Apolipoprotein F emerges as a natural, LDL-selective inhibitor of CETP (Curr Opin Lipidol 2020)
Original title: Apolipoprotein F: a natural inhibitor of cholesteryl ester transfer protein and a key regulator of lipoprotein metabolism
This review examines apolipoprotein F (ApoF), a minor apolipoprotein now understood to be a natural inhibitor of cholesteryl ester transfer protein (CETP). Recent work shows ApoF hepatic mRNA is suppressed by fat-enriched diets through agonist-induced binding of liver X receptor and PPARalpha to its promoter, and that ApoF lowers LDL cholesterol and enhances reverse cholesterol transport in fat-fed hamsters. Unlike a general CETP inhibitor, ApoF preferentially blocks CETP activity specifically with LDL, tailoring CETP so that less HDL-derived cholesterol traffics into the LDL compartment. Given the clinical failures of pharmacological CETP inhibitors, the authors suggest this LDL-selective, endogenous mode of CETP inhibition may offer a more favourable therapeutic angle than global CETP blockade.
Original 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.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.