Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/82215
Title: Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism
Authors: Rando, Gianpaolo
Tan, Chek Kun
Khaled, Nourhène
Montagner, Alexandra
Leuenberger, Nicolas
Bertrand-Michel, Justine
Paramalingam, Eeswari
Guillou, Hervé
Wahli, Walter
Keywords: PPARα
lipid catabolism
Issue Date: 2016
Source: Rando, 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-.
Series/Report no.: eLife
Abstract: In 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.
URI: https://hdl.handle.net/10356/82215
http://hdl.handle.net/10220/41171
DOI: 10.7554/eLife.11853
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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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