Study Title:

B Vitamins Help Prevent Programmed Obesity

Study 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.

From LA Times article:,0,1654700.story

Weight gain halted by vitamins, study of mice finds

A diet supplemented with folic acid, vitamin B-12 and other additives appears to block a gene and prevent successive generations of mice from getting fatter, researchers report.

By Wendy Hansen, Los Angeles Times Staff Writer

July 19, 2008

Scientists have used a special blend of vitamins and nutrients to stop successive generations of mice from becoming progressively more overweight.

The researchers looked at three generations of genetically identical mice that were prone to obesity and found that the offspring got heavier even though they were fed the same diet as their mothers.

But the mice didn't get any plumper when that diet was supplemented with folic acid, vitamin B-12, choline and betaine, according to a study published Tuesday in the International Journal of Obesity.

Because the genetic makeup of the mice was the same, the scientists concluded that the diet supplements had managed to suppress the activity of key genes related to obesity.

Dr. Robert Waterland, an assistant professor of pediatrics in the Children's Nutrition Research Center at Baylor College of Medicine in Houston and lead author of the study, said that the supplements are known to promote methylation, a process of chemically tagging DNA that suppresses genes.

Such influences, termed epigenetic because they stem from factors outside of the genome, play a major role in development.

"The entire genome is in nearly all of our cells and yet our liver cells express a very different set of genes than the cells in our gut," Waterland said.

Epigenetic effects are known to contribute to cancer, but their influence on weight regulation is an open question.

"Everybody knows that what pregnant women eat matters for their children," said Craig Warden, a professor of pediatrics and genetics at UC Davis who was not involved in the study.

"This could be part of that story."

Waterland said that methylation may affect development of the hypothalamus, a region of the brain that controls appetite, and he plans to research this in both mice and humans.

Although people lack the gene that originally made the mice obese, the study "makes a nice parallel with humans because we know that a lot of humans have a genetic predisposition to obesity, especially in the current environment of food excess," Waterland said.

Study Information

Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S.
Methyl donor supplementation prevents transgenerational amplification of obesity.
Int J Obes (Lond).
2008 July
Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, USDA Children's Nutrition Research Center, Houston, TX, USA.

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