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Glucocorticoid receptor-PPAR? axis in fetal mouse liver prepares neonates for milk lipid catabolism.

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 PPAR?, 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)-PPAR? axis in which GR directly regulates the transcriptional activation of PPAR? by binding to its promoter. Certain PPAR? target genes such as Fgf21 remain repressed in the fetal liver and become PPAR? responsive after birth following an epigenetic switch triggered by ?-hydroxybutyrate-mediated inhibition of HDAC3. This study identifies an endocrine developmental axis in which fetal GR primes the activity of PPAR? in anticipation of the sudden shifts in postnatal nutrient source and metabolic demands.

SUBMITTER: Rando G

PROVIDER: S-EPMC4963200 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism.

Rando Gianpaolo G Tan Chek Kun CK Khaled Nourhène N Montagner Alexandra A Leuenberger Nicolas N Bertrand-Michel Justine J Paramalingam Eeswari E Guillou Hervé H Wahli Walter W

eLife 20160701

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 ...[more]

PMID: 27367842

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Dataset Information

Glucocorticoid receptor-PPAR? axis in fetal mouse liver prepares neonates for milk lipid catabolism.

Publications

Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism.

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