Feb 13, 2018

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

Nature Communications
Xunmei YuanYoshihiro Ogawa

Abstract

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity.

  • References52
  • Citations6

References

  • References52
  • Citations6

Citations

Mentioned in this Paper

PPARA
PPARA wt Allele
DNA Methylation [PE]
Diet
Peroxisome Proliferator-Activated Receptors
Protein Methylation
Genome
DNA Methylation
Hepatic
Fibroblast Growth Factor Binding

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