Figure 2 – Effect of ApoF on the fate of HDL CE.

CE in HDL can be transferred to VLDL and LDL by CETP. LDL and VLDL are cleared by separate hepatic receptor mechanisms. ApoF preferentially blocks CETP activity on LDL, thus reducing the flow of HDL derived CE along this pathway. For both panels, arrow size reflects relative CETP activity between the indicated lipoprotein pairs. Panel A - In chow-fed animals, depletion of ApoF increases CE transfer to LDL. Since hepatic LDL receptor activity is high, the increased CE in LDL is efficiently delivered to the liver, thus increasing the overall delivery of HDL CE to the liver and preventing LDL cholesterol from rising. Panel B - In fat-fed animals, LDL-associated ApoF is increased by the diet, which further reduces the transfer of HDL CE to LDL compared to chow-fed animals. When ApoF is depleted, overall CE efflux from HDL is increased, but due to its initial greater repression by ApoF, CE transfer to LDL is markedly increased. However, since hepatic LDL receptor levels are low in fat-fed animals, HDL-derived CE accumulates in LDL. This results in an overall decrease in HDL CE delivery to the liver. Direct HDL CE clearance by SR-BI is not shown in these models. Abbreviations: LDLR, low density lipoprotein receptor; HSPG, heparan sulfate proteoglycans.