Mechanisms
Low CETP activity late in pregnancy, in mother and placenta alike, is linked to giving birth to small-for-gestational-age infants (Sci Rep 2021)
Original title: Low CETP activity and unique composition of large VLDL and small HDL in women giving birth to small-for-gestational age infants
Since HDL cholesterol, regulated by CETP, is important for fetal development, this study measured circulating lipids and CETP activity across pregnancy and performed NMR lipidomics and RNA sequencing of 28 placentas to compare mothers giving birth to large-for-gestational-age (LGA) versus small-for-gestational-age (SGA) infants. Women who gave birth to SGA infants had high triglycerides in large VLDL particles and high lipid, cholesterol and cholesteryl ester content in small HDL. Placentas from mothers with higher circulating HDL-C had lower CETP expression, which correlated with mRNAs involved in cholesterol and nutrient transport, insulin signalling, and inflammation and extracellular matrix remodelling. Both placental and circulating CETP levels tracked with fetal growth, and low circulating CETP activity at 36 to 38 weeks was associated with delivering an SGA infant. The authors propose a link between higher maternal HDL-C, lower CETP activity in circulation and placenta, and impaired fetal growth, a reproductive-medicine application of CETP biology outside cardiovascular disease.
Original abstract
Cholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol (C) and HDL-C is essential for fetal development. We hypothesized that women giving birth to large-for-gestational-age (LGA) and small-for-gestational age (SGA) infants differed in longitudinal changes in lipoproteins, CETP activity and HDL-C and that placentas from women with higher or lower circulating HDL-C displayed differential expression of mRNAs involved in cholesterol/nutrient transport, insulin signaling, inflammation/ extracellular matrix (ECM) remodeling. Circulating lipids and CETP activity was measured during pregnancy, NMR lipidomics in late pregnancy, and associations with LGA and SGA infants investigated. RNA sequencing was performed in 28 placentas according to higher and lower maternal HDL-C levels. Lipidomics revealed high triglycerides in large VLDL and lipids/cholesterol/cholesteryl esters in small HDL in women giving birth to SGA infants. Placentas from women with higher HDL-C had decreased levels of CETP expression which was associated with mRNAs involved in cholesterol/nutrient transport, insulin signaling and inflammation/ECM remodeling. Both placental and circulating CETP levels were associated with growth of the fetus. Low circulating CETP activity at 36-38 weeks was associated with giving birth to SGA infants. Our findings suggest a link between increased maternal HDL-C levels, low CETP levels both in circulation and placenta, and SGA infants.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.