Mechanisms
CETP-deficient cells cannot efficiently convert diglyceride into stored triglyceride (J Lipid Res 2015)
Original title: Defective triglyceride biosynthesis in CETP-deficient SW872 cells
Reducing CETP expression in SW872 cells was previously shown to disrupt cholesterol homeostasis and cut triglyceride content by about 50 percent. Investigating why, researchers found the reduction was not explained by altered cell differentiation or endoplasmic reticulum (ER) stress, and the total flux of oleate through the triglyceride biosynthetic pathway was unchanged in the short term, though the conversion of diglyceride to triglyceride was impaired. In longer-term studies, newly synthesised triglyceride was not effectively transported to lipid droplets, but did not accumulate in the ER due to elevated local lipase activity, and diglyceride, identified here as a novel CETP substrate, was also poorly transferred to lipid droplets. The findings indicate CETP deficiency reduces triglyceride content through impaired diglyceride-to-triglyceride conversion and enhanced ER triglyceride degradation.
Original abstract
We previously reported that reducing the expression of cholesteryl ester transfer protein (CETP) disrupts cholesterol homeostasis in SW872 cells and causes an ∼50% reduction in TG. The causes of this reduced TG content, investigated here, could not be attributed to changes in the differentiation status of CETP-deficient cells, nor was there evidence of endoplasmic reticulum (ER) stress. In short-term studies, the total flux of oleate through the TG biosynthetic pathway was not altered in CETP-deficient cells, although mRNA levels of some pathway enzymes were different. However, the conversion of diglyceride (DG) to TG was impaired. In longer-term studies, newly synthesized TG was not effectively transported to lipid droplets, yet this lipid did not accumulate in the ER, apparently due to elevated lipase activity in this organelle. DG, shown to be a novel CETP substrate, was also inefficiently transferred to lipid droplets. This may reduce TG synthesis on droplets by resident diacylglycerol acyltransferase. Overall, these data suggest that the decreased TG content of CETP-deficient cells arises from the reduced conversion of DG to TG in the ER and/or on the lipid droplet surface, and enhanced TG degradation in the ER due to its ineffective transport from this organelle.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.