In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-07-01)
Abstract:
Birth is a highly stressful and critical event. In the womb, babies rely on the supply of oxygen and nutrients provided by the placenta. However, once they are born they need to breathe for themselves and gain all their nutrients from suckling milk. The placenta provides a sugar-rich diet, while milk is richer in fat. Failing to cope with this change in diet leads to serious complications and sometimes death. Therefore, a better understanding of how the body adapts to these changes may shed light on pathways that are important for good health in later life. The liver plays a central role in processing the nutrients absorbed by the gut. It uses fats to produce molecules called ketone bodies, such as β-hydroxybutyrate, which are then used as fuel by other tissues and organs including the heart, muscle and the brain. A protein called PPARα controls the production of ketone bodies primarily by regulating genes that are involved in the uptake and breakdown of fat in the liver. However, little is known about how this protein affects the development of the liver. Here, Rando, Tan et al. report that mice start to produce more PPARα in the liver shortly before birth. This ultimately activates several genes that encode enzymes that break down fats. The experiments show that during labor, stress hormones called glucocorticoids directly stimulate the production of PPARα in the liver of the fetus to prepare newborn mice for harnessing energy from fat-rich milk. In the absence of PPARα, mouse liver cells are less able to break down fats after birth and so start to accumulate fat, resulting in fewer ketone bodies being produced. Rando, Tan et al. show that β-hydroxybutyrate regulates some PPARα target genes, including one called Fgf21. The activity of this gene increases only after milk suckling starts and it encodes a protein that enhances the breakdown of fats in the liver. Without PPARα, the expression levels of its target genes, including Fgf21, do not increase after birth, which promotes the build up of fats in liver cells, a condition known as liver steatosis. Overall, the results reported by Rando, Tan et al. highlight how stress during labor plays an important role in priming the body to cope with a fat-rich diet after birth. Future studies will need to determine if stress hormones and ketone bodies could be used as therapies for babies born by caesarean section with liver steatosis.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.11853.001
DOI:
10.7554/eLife.11853.002
DOI:
10.7554/eLife.11853.003
DOI:
10.7554/eLife.11853.004
DOI:
10.7554/eLife.11853.005
DOI:
10.7554/eLife.11853.006
DOI:
10.7554/eLife.11853.007
DOI:
10.7554/eLife.11853.008
DOI:
10.7554/eLife.11853.009
DOI:
10.7554/eLife.11853.010
DOI:
10.7554/eLife.11853.011
DOI:
10.7554/eLife.11853.012
DOI:
10.7554/eLife.11853.013
DOI:
10.7554/eLife.11853.014
DOI:
10.7554/eLife.11853.015
DOI:
10.7554/eLife.11853.016
DOI:
10.7554/eLife.11853.017
DOI:
10.7554/eLife.11853.018
DOI:
10.7554/eLife.11853.019
DOI:
10.7554/eLife.11853.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
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