ESPEYB15 15 Editor’s Choice Memories that persist into adulthood (1 abstracts)
15.14 Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood
Yuan X , Tsujimoto K , Hashimoto K , Kawahori K , Hanzawa N , Hamaguchi M , Seki T , Nawa M , Ehara T & Kitamura Y
To read the full abstract: Nature Communications 2018;9:636
We know that good nutrition early in life has profound and long-lasting effects on body weight in later life. Malnutrition during pregnancy or infant formula feeding may be stored on the offspring genome as epigenetic memory and persist into adulthood, thereby influencing the susceptibility to metabolic diseases, such as obesity in later life.
These authors had previously found that, during lactation, milk lipids serve as a ligand to activate PPARα and its effect on liver fat metabolism. They also demonstrated that administration of a synthetic PPARα ligand to mouse dams during the perinatal period reduced DNA methylation of fatty-acid β-oxidation genes in the liver of the offspring. Here, using a genome-wide DNA methylation analysis, they identified the liver hormone Fgf21 as a PPARα target gene for DNA demethylation during the perinatal period, which persists into adulthood to exert long-term effects on gene expression in response to environmental cues. This may account in part for the attenuation of diet-induced obesity. Other than the Fgf21 story, this study represents the first analysis of DNA methylation of a gene throughout life. It provides the proof of concept of epigenetic modulation in early life, through which the epigenetic status of a gene can be modified during the suckling period, and provides a critical time window to establish epigenetic memory, as according to the DOHaD hypothesis. Fgf21 regulates monosaccharide intake and preferences for sweet foods via signaling through FGF21 receptors in the suprachiasmatic nucleus and paraventricular nucleus of the hypothalamus. We now know that this pathway is epigenetically regulated during breastfeeding.
Volume 15
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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