Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27367842.
- Also identified by DOI 10.7554/eLife.11853 and PMC identifier 4963200.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Gene Expression Regulation, Developmental
- Lipid Metabolism
- Liver
- Metabolism
- Milk
- PPAR alpha
- Receptors, Glucocorticoid