Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Int J Obes (Lond). 2008 Sep;32(9):1373-9. doi: 10.1038/ijo.2008.100. Epub 2008 Jul 15.

Methyl donor supplementation prevents transgenerational amplification of obesity.

Author information

  • 1Department of Pediatrics, Baylor College of Medicine, USDA Children's Nutrition Research Center, Houston, TX 77030, USA. waterland@bcm.edu

Abstract

BACKGROUND:

The obesity epidemic, recognized in developed nations for decades, is now a worldwide phenomenon. All age groups are affected, including women of childbearing age, fueling concern that maternal obesity before and during pregnancy and lactation impairs developmental establishment of body weight regulatory mechanisms in the fetus or infant, causing transgenerational amplification of obesity prevalence and severity. The biological mechanisms underlying such processes remain unknown.

METHODS:

We used agouti viable yellow (A(vy)) mice to test the hypothesis that maternal obesity induces transgenerational amplification of obesity. We passed the A(vy) allele through three generations of A(vy)/a females and assessed cumulative effects on coat color and body weight. By studying two separate but contemporaneous populations of mice, one provided a standard diet and the other a methyl-supplemented diet that induces DNA hypermethylation during development, we tested whether potential transgenerational effects on body weight might be mediated by alterations in epigenetic mechanisms including DNA methylation.

RESULTS:

The genetic tendency for obesity in A(vy) mice was progressively exacerbated when the A(vy) allele was passed through successive generations of obese A(vy) females. This transgenerational amplification of body weight was prevented by a promethylation dietary supplement. Importantly, the effect of methyl supplementation on body weight was independent of epigenetic changes at the A(vy) locus, indicating this model may have direct relevance to human transgenerational obesity.

CONCLUSION:

Our results show that in a population with a genetic tendency for obesity, effects of maternal obesity accumulate over successive generations to shift the population distribution toward increased adult body weight, and suggest that epigenetic mechanisms are involved in this process.

PMID:
18626486
[PubMed - indexed for MEDLINE]
PMCID:
PMC2574783
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk