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dc.contributor.authorRando, Gianpaoloen
dc.contributor.authorTan, Chek Kunen
dc.contributor.authorKhaled, Nourhèneen
dc.contributor.authorMontagner, Alexandraen
dc.contributor.authorLeuenberger, Nicolasen
dc.contributor.authorBertrand-Michel, Justineen
dc.contributor.authorParamalingam, Eeswarien
dc.contributor.authorGuillou, Hervéen
dc.contributor.authorWahli, Walteren
dc.identifier.citationRando, G., Tan, C. K., Khaled, N., Montagner, A., Leuenberger, N., Bertrand-Michel, J., et al. (2016). Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism. eLife, 5, e11853-.en
dc.description.abstractIn mammals, hepatic lipid catabolism is essential for the newborns to efficiently use milk fat as an energy source. However, it is unclear how this critical trait is acquired and regulated. We demonstrate that under the control of PPARα, the genes required for lipid catabolism are transcribed before birth so that the neonatal liver has a prompt capacity to extract energy from milk upon suckling. The mechanism involves a fetal glucocorticoid receptor (GR)-PPARα axis in which GR directly regulates the transcriptional activation of PPARα by binding to its promoter. Certain PPARα target genes such as Fgf21 remain repressed in the fetal liver and become PPARα responsive after birth following an epigenetic switch triggered by β-hydroxybutyrate-mediated inhibition of HDAC3. This study identifies an endocrine developmental axis in which fetal GR primes the activity of PPARα in anticipation of the sudden shifts in postnatal nutrient source and metabolic demands.en
dc.format.extent31 p.en
dc.rights© Rando et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en
dc.subjectlipid catabolismen
dc.titleGlucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolismen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.description.versionPublished versionen
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