HDL biology
Advanced mass spectrometry reveals that CETP is secreted in medium-large HDL and stays there, unlike LCAT which appears on HDL only after a delay (JCI Insight 2021)
Original title: Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos
Building on prior targeted mass spectrometry tracer studies of HDL proteins, this study showed that the Orbitrap Fusion Lumos can measure tracer enrichment in proteins thousands-fold less abundant than apolipoprotein A1, including phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT). Relative to the Q Exactive instrument, the Lumos reduced tracer enrichment compression, providing consistent data across multiple HDL sizes from 6 participants. Compartmental modeling showed that PLTP is secreted in medium and large HDL and transfers to larger sizes during circulation before catabolism, while CETP is secreted mainly in the alpha1 and alpha2 HDL sizes and remains there during circulation. LCAT, unlike PLTP and CETP, appears on HDL only after a marked delay, suggesting it may reside outside systemic circulation before attaching to HDL in plasma.
Original abstract
Recent in vivo tracer studies demonstrated that targeted mass spectrometry (MS) on the Q Exactive Orbitrap could determine the metabolism of HDL proteins 100s-fold less abundant than apolipoprotein A1 (APOA1). In this study, we demonstrate that the Orbitrap Lumos can measure tracer in proteins whose abundances are 1000s-fold less than APOA1, specifically the lipid transfer proteins phospholipid transfer protein (PLTP), cholesterol ester transfer protein (CETP), and lecithin-cholesterol acyl transferase (LCAT). Relative to the Q Exactive, the Lumos improved tracer detection by reducing tracer enrichment compression, thereby providing consistent enrichment data across multiple HDL sizes from 6 participants. We determined by compartmental modeling that PLTP is secreted in medium and large HDL (alpha2, alpha1, and alpha0) and is transferred from medium to larger sizes during circulation from where it is catabolized. CETP is secreted mainly in alpha1 and alpha2 and remains in these sizes during circulation. LCAT is secreted mainly in medium and small HDL (alpha2, alpha3, prebeta). Unlike PLTP and CETP, LCAT's appearance on HDL is markedly delayed, indicating that LCAT may reside for a time outside of systemic circulation before attaching to HDL in plasma. The determination of these lipid transfer proteins' unique metabolic structures was possible due to advances in MS technologies.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.