Mechanisms
Chronic CETP deficiency disrupts adipocyte lipid storage, revealing a novel intracellular role for CETP (J Biol Chem 2007)
Original title: Possible role for intracellular cholesteryl ester transfer protein in adipocyte lipid metabolism and storage
SW872 adipocytes engineered to stably express antisense CETP cDNA and synthesize 20% of normal CETP developed 4-fold more cholesteryl ester but roughly 3-fold less cholesterol biosynthesis, alongside a 45% reduction in LDL receptor and 2.5-fold rise in ABCA1, consistent with cellular cholesterol overload, even though total cholesterol mass was actually reduced. CETP-deficient adipocytes stored less than 50% of normal triglyceride, mainly from reduced synthesis, with cellular cholesteryl ester and triglyceride hydrolysis reduced more than 50% despite 3-fold higher hydrolase/lipase activity, and incorporation of newly synthesized lipids into storage droplets fell to just 40% of control. In vitro assays directly confirmed cellular CETP transports cholesteryl ester and triglyceride into storage droplets, supporting a novel intracellular role for CETP in lipid transport and storage beyond its plasma lipoprotein function.
Original abstract
Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) and triglyceride (TG) between lipoproteins in plasma. However, short term suppression of CETP biosynthesis in cells alters cellular cholesterol homeostasis, demonstrating an intracellular role for CETP as well. The consequences of chronic CETP deficiency in lipid-storing cells normally expressing CETP have not been reported. Here, SW872 adipocytes stably expressing antisense CETP cDNA and synthesizing 20% of normal CETP were created. CETP-deficient cells had 4-fold more CE but an approximately 3-fold decrease in cholesterol biosynthesis. This phenotype of cholesterol overload is consistent with the observed 45% reduction in low density lipoprotein receptor and 2.5-fold increase in ABCA1 levels. However, cholesterol mass in CETP-deficient adipocytes was actually reduced. Strikingly, CETP-deficient adipocytes stored <50% of normal TG, principally reflecting reduced synthesis. The hydrolysis of cellular CE and TG in CETP-deficient cells was reduced by >50%, although hydrolase/lipase activity was increased 3-fold. Notably, the incorporation of recently synthesized CE and TG into lipid storage droplets in CETP-deficient cells was just 40% of control, suggesting that these lipids are inefficiently transported to droplets where the hydrolase/lipase resides. The capacity of cellular CETP to transport CE and TG into storage droplets was directly demonstrated in vitro. Overall, chronic CETP deficiency disrupts lipid homeostasis and compromises the TG storage function of adipocytes. Inefficient CETP-mediated translocation of CE and TG from the endoplasmic reticulum to their site of storage may partially explain these defects. These studies in adipocytic cells strongly support a novel role for CETP in intracellular lipid transport and storage.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.