Modulation of Fgf21 gene in early-life ameliorates adulthood diet-induced obesity

March 12, 2018, Tokyo Medical and Dental University
The DNA methylation status of Fgf21, once established in early life, affects obesity in adulthood. Credit: Department of Molecular Endocrinology and Metabolism

The importance of good nutrition in the early development of children has been recognized for many decades. Nutritional experiences in early life can have profound and long-lasting effects on body weight in later life. For instance, malnutrition in early life as a result of poor nutrition during pregnancy and/or the lactation period may cause epigenetic changes that persist into adulthood, thereby increasing the susceptibility to metabolic diseases such as obesity in later life. This area of epigenetics has become one of the fastest-growing and most complex areas of biological science.

A team of researchers led by Tokyo Medical and Dental University (TMDU) previously found that upon the onset of lactation after birth, milk lipids serve as a ligand to activate the nuclear receptor peroxisome proliferator-activated receptor (PPAR)α, which is a key transcriptional regulator of liver fat metabolism. They also demonstrated that administration of a synthetic PPARα ligand to mouse dams during the perinatal period induces enhanced reductions in DNA methylation of fatty-acid β-oxidation in the liver of the offspring. DNA methylation is an epigenetic mechanism used by cells to control .

These findings prompted the researchers to explore whether DNA methylation status of PPARα target genes, which is modulated and established in a PPARα-dependent manner in , persists into adulthood.

"In the current study, using a genome-wide analysis of DNA methylation, we identified a few PPARα target genes that underwent ligand-activated PPARα-dependent DNA demethylation during the and whose DNA methylation status persists into adulthood," says corresponding author Koshi Hashimoto . "We provide the first evidence that the PPARα-dependent gene Fgf21 demethylation occurs in the postnatal mouse liver, and once established it persists into adulthood and exerts long-term effects on the magnitude of gene expression response to environmental cues, which may account in part for the attenuation of diet-induced obesity."

This study represents the first detailed analysis of DNA methylation status of a particular gene throughout life, and the results were recently published in Nature Communications.

"Given that PPARα may act as a sensor of milk lipids during the suckling period, it is likely that the suckling period provides a critical time window for PPARα-dependent Fgf21 demethylation in response to the maternal environment," adds senior author Yoshihiro Ogawa. "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."

Explore further: Protein may improve liver regeneration

More information: Xunmei Yuan et al, Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood, Nature Communications (2018). DOI: 10.1038/s41467-018-03038-w

Related Stories

Protein may improve liver regeneration

March 31, 2015
Researchers at UC Davis have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPARα, which activates liver regeneration. Normally, mouse PPARα ...

Maternal diet may program child for disease risk, but better nutrition later can change that

October 20, 2017
Research has shown that a mother's diet during pregnancy, particularly one that is high-fat, may program her baby for future risk of certain diseases such as diabetes. A new study from nutrition researchers at the University ...

Epigenetic rheostat uncovers how gene regulation is inherited and maintained

December 15, 2017
While our genome contains a vast repertoire of genes that are responsible for virtually all of the cellular and developmental processes life requires, it is the complex dance of regulating their expression that is vital for ...

Risk of obesity influenced by changes in our genes

April 25, 2017
These changes, known as epigenetic modifications, control the activity of our genes without changing the actual DNA sequence. One of the main epigenetic modifications is DNA methylation, which plays a key role in embryonic ...

Immune diseases inflict identical twins differently

December 13, 2017
Any parent with identical twins knows their two children are actually remarkably different. Identical twins are genetically identical, but they are not identical in gene expressions, a difference attributable to epigenetics. ...

Prenatal infection may alter brain development via epigenetic changes

January 24, 2017
Maternal infection during pregnancy increases the risk for psychiatric disorders in the child, but the path between the two is something of a mystery. In a study published in Biological Psychiatry, senior author Professor ...

Recommended for you

Geneticists make new discovery about how a baby's sex is determined

December 14, 2018
Medical researchers at Melbourne's Murdoch Children's Research Institute have made a new discovery about how a baby's sex is determined—it's not just about the X-Y chromosomes, but involves a 'regulator' that increases ...

Scientists identify method to study resilience to pain

December 14, 2018
Scientists at the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System have successfully demonstrated that it is possible to pinpoint genes that contribute to inter-individual differences in pain.

CRISPR joins battle of the bulge, fights obesity without edits to genome

December 13, 2018
A weighty new study shows that CRISPR therapies can cut fat without cutting DNA. In a paper published Dec. 13, 2018, in the journal Science, UC San Francisco researchers describe how a modified version of CRISPR was used ...

Noncoding mutations contribute to autism risk

December 13, 2018
A whole-genome sequencing study of nearly 2,000 families has implicated mutations in 'promoter regions' of the genome—regions that precede the start of a gene—in autism. The study, which appears in the December 14 issue ...

New method for studying ALS more effectively

December 13, 2018
The neurodegenerative disease ALS causes motor neuron death and paralysis. However, long before the cells die, they lose contact with muscles as their axons atrophy. Researchers at Karolinska Institutet in Sweden have now ...

Paternal grandfather's high access to food may indicate higher mortality risk in grandsons

December 12, 2018
A paternal grandfather's access to food during his childhood is associated with mortality risk, especially cancer mortality, in his grandson, shows a large three-generational study from Stockholm University. The reason might ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.