King's College London

Research portal

Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis

Research output: Contribution to journalArticle

Vanya Nikolova, Georgia Papacleovoulou, Elena Bellafante, Luiza Borges Manna, Eugene Jansen, Silvère Baron, Shadi Abu-Hayyeh, Malcolm G Parker, Catherine Williamson

Original languageEnglish
Pages (from-to)ajpendo.00449.2016
JournalAMERICAN JOURNAL OF PHYSIOLOGY: ENDOCRINOLOGY AND METABOLISM
Early online date18 Apr 2017
DOIs
Publication statusPublished - Oct 2017

Documents

King's Authors

Abstract

Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors which stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and LXRα, β(-/-) mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis which is also necessary to protect against abnormalities in fetoplacental lipid homeostasis.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454