Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Borges Manna, Luiza
MetadataShow full item record
TitleChanges in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.
Published inAm J Physiol Endocrinol Metab 2017; 313(4):E463-72
PubliekssamenvattingHuman 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 that 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 Lxrab-/- 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 that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis.
- Fetal liver X receptor activation acutely induces lipogenesis but does not affect plasma lipid response to a high-fat diet in adult mice.
- Authors: van Straten EM, van Meer H, Huijkman NC, van Dijk TH, Baller JF, Verkade HJ, Kuipers F, Plösch T
- Issue date: 2009 Nov
- Liver X receptor activation increases hepatic fatty acid desaturation by the induction of SCD1 expression through an LXRα-SREBP1c-dependent mechanism.
- Authors: Zhang X, Liu J, Su W, Wu J, Wang C, Kong X, Gustafsson JÅ, Ding J, Ma X, Guan Y
- Issue date: 2014 May
- Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor-driven transcription of hepatic lipogenic genes in vivo.
- Authors: Nahon JE, Groeneveldt C, Geerling JJ, van Eck M, Hoekstra M
- Issue date: 2018 Aug
- Ursodeoxycholic acid inhibits liver X receptor α-mediated hepatic lipogenesis via induction of the nuclear corepressor SMILE.
- Authors: Lee JM, Gang GT, Kim DK, Kim YD, Koo SH, Lee CH, Choi HS
- Issue date: 2014 Jan 10
- The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR.
- Authors: Cha JY, Repa JJ
- Issue date: 2007 Jan 5