Yan Liu1, Richard E Morton. 1. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
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.
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.
Authors: M Guérin; W Le Goff ; T S Lassel; A Van Tol ; G Steiner; M J Chapman Journal: Arterioscler Thromb Vasc Biol Date: 2001-02 Impact factor: 8.311
Authors: William R Lagor; David W Fields; Sumeet A Khetarpal; Arthi Kumaravel; Wen Lin; Nathaniel Weintraub; Kaijin Wu; Sarah F Hamm-Alvarez; Denise Drazul-Schrader; Margarita de la Llera-Moya; George H Rothblat; Daniel J Rader Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240