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Updated: Sep 16, 2025
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Cholesterol Efflux Assay
Published on: March 6, 2012
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Cholesteryl ester transfer protein activity correlates inversely with apolipoprotein A5 levels
Yi Wen1, Hongxia Li1, Sydney Smith1
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA (Drs Wen, Li, Smith, Lin, Chen, Bellinger, Zhen, Beyer, Siegel, Qian, Ruotolo, and Konrad).
Journal of Clinical Lipidology
|July 8, 2025
Summary
Cholesteryl ester transfer protein (CETP) overexpression lowers apolipoprotein A5 (ApoA5), while CETP inhibition raises ApoA5 levels. This study reveals a new connection between CETP and ApoA5 regulation in lipid metabolism.
Area of Science:
- Lipid metabolism and cardiovascular research.
- Endocrinology and lipoprotein biology.
Background:
- Cholesteryl ester transfer protein (CETP) facilitates lipid exchange between lipoproteins, influencing HDL-C and LDL-C levels.
- CETP inhibition increases HDL-C and decreases LDL-C, but its effect on triglycerides (TG) is complex, as it inhibits TG removal from TG-rich lipoproteins.
- Lipoprotein lipase (LPL) hydrolyzes TG, and its activity is regulated by the ANGPTL3/8 complex (inhibitor) and apolipoprotein A5 (ApoA5) (suppressor of inhibition).
Purpose of the Study:
- To elucidate the relationship between CETP activity and the levels of ANGPTL3/8 and ApoA5.
- To investigate the impact of CETP overexpression and inhibition on circulating ANGPTL3/8 and ApoA5.
Main Methods:
- Utilized dedicated immunoassays to measure ANGPTL3/8 and ApoA5 levels.
- Studied CETP-overexpressing transgenic mice.
- Administered the CETP inhibitor evacetrapib to mice and human subjects.
Main Results:
- CETP overexpression in mice led to increased TG, normal ANGPTL3/8, and significantly reduced ApoA5 levels.
- Evacetrapib treatment did not alter ANGPTL3/8 levels in mice or humans.
- Evacetrapib administration markedly increased ApoA5 concentrations in both mice and humans, with substantial increases observed in human clinical trials (ACCELERATE and ACCENTUATE).
Conclusions:
- Demonstrated a novel inverse relationship between CETP activity and ApoA5 levels.
- CETP overexpression downregulates ApoA5, whereas CETP inhibition upregulates ApoA5.
- These findings provide new insights into the regulation of lipid metabolism and potential therapeutic targets.
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