The FGF21 gene, which has an effect of improving glycolipid metabolism, undergoes DNA demethylation due to the components of breast milk in infancy, and the once established DNA methylation state is memorized and maintained (epigenome memory) for a long period of time, resulting in obesity in adulthood. It became clear that it was related to the onset.This is the result of joint research between a research group led by Professor Yoshihiro Ogawa of Tokyo Medical and Dental University and Kyushu University, and Tsukuba University and Morinaga Milk Industry.
If the pregnant mother is overnourished or undernourished, the child born is at increased risk of developing lifestyle-related diseases in adulthood (DOHaD hypothesis).As the molecular mechanism of this hypothesis, "epigenome modification" (Note) by "DNA methylation" of metabolism-related genes is drawing attention.
In this study, we found that the FGF21 gene, which has an effect of improving glycolipid metabolism, undergoes DNA demethylation mediated by the lipid sensor molecule PPARα in the liver of mice in infancy.In addition, when a drug that activates PPARα is administered to lactating mother animal mice, this is transferred to milk, and DNA demethylation of the FGF21 gene is further promoted in milk-fed offspring mice. It was clarified that the once established DNA methylation state is memorized and maintained for a long period of time until the adult stage.
On the other hand, the promotion of DNA demethylation did not occur even when the drug was administered during the adult period, and was limited to the infancy period.In addition, in offspring mice with advanced DNA demethylation of the FGF21 gene, the expression level of the FGF21 gene is more strongly induced by activation of PPARα in the adult stage, and even if a high-fat diet is fed in the adult stage, FGF21 It was found that the progression of obesity was suppressed as the expression level of the gene increased.
By suggesting the molecular mechanism by which epigenome memory in infancy is associated with the onset of disease in adulthood, it is expected that clues to "preemptive medicine" for lifestyle-related diseases that intervene in infancy will be obtained.
(Note) The mechanism that acquires the expression level of a gene without changing the gene itself is called epigenome modification. DNA methylation is one of the typical epigenome modifications and usually suppresses gene expression.
Paper information:[Nature Communications] Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood
