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S.F. Ng, et al., " Chronic high-fat diet in fathers programs B-cell dysfunction

in female rat offspring, " Nature, 467:963-7, 2010.

A father's high-fat diet may increase his offspring's risk of diabetes, evidence

suggests

[Published 20th October 2010 06:00 PM GMT]

A father's diet can directly affect his daughter's health, according to a study

in rats published today (October 20) in Nature.

For the first time, researchers have demonstrated a purported epigenetic link

between a father's high-fat diet and an increased risk of disease in his

offspring -- in this case, diabetes.

Numerous papers have shown that aspects of a mother's health, including her

weight, can have a significant impact on her offspring, but few have shown the

same effect on the paternal side. " It really does bring the father into play, "

said Skinner, a researcher at the Center for Reproductive Biology at

Washington State University, who was not involved in the study.

" This outcome suggests that our predisposition toward disease can be affected by

what our parents or grandparents consumed during key points in their

development, " Bale of the University of Pennsylvania said in an email.

Bale, who was also not involved in the research, published a complementary study

last year showing that a maternal high-fat diet can affect two generations of

offspring.

Margaret , a researcher at the University of New South Wales in Sydney,

Australia, and senior author on the paper, decided to test the idea after

wondering about the male rats in some of her obesity studies. " I could see their

prostates getting bigger and I thought, 'Boy, what's this doing to their

reproductive function?' " said . Together with Sheau-Fang Ng, a pediatric

endocrinologist in the lab intrigued by obese families she regularly witnessed

in the clinic, set out to see if there was some non-genetic transmission

of traits from an obese father to his offspring.

Male rats were started on a high-fat diet -- 40 percent more calories than

control rats -- prior to puberty at 4 weeks old and kept on the diet for 12

weeks. The rats became obese and began developing diabetes, including glucose

intolerance and high resting levels of insulin.

After the rats were mated, the researchers analyzed the offspring, gestated in

normal females. Early evidence suggested female offspring are more susceptible

to paternal effects, so the team focused on female pups. By 6 weeks old, the

young female rats were glucose intolerant. By 12 weeks of age, they had impaired

insulin secretion. When the rats were dissected at 12-14 weeks, they had a

noticeable decrease in islet mass, or insulin-secreting cells in the pancreas,

relative to control offspring.

Additional research showed that the paternal high-fat diet actually altered gene

expression in female offspring, changing expression patterns for 642 pancreatic

islet genes and numerous others involved in signaling and apoptosis pathways.

" That might be relevant to why we have a loss of islets " in female pups,

told The Scientist.

Presumably, the effects of a high-fat diet -- most likely epigenetic changes

such as DNA methylation or histone modification, believes -- were passed

from father to daughter through the father's sperm. " We really have to look at

the sperm here. The sperm is the elephant in the room, " said .

Germ line cells are just as susceptible to environmental factors as other cells

in the body, and if they undergo changes, " it can have dramatic effects, not

only for the immediate offspring, but also subsequent progeny, " said Skinner,

author of an accompanying News & Views article in this week's Nature.

Future studies still need to test whether the father's diet can affect future

generations and if the same holds true in human populations, said . " We

have to be a little bit cautious, because clearly it is a rat study, " she added,

" but this paper does tell us something about the sorts of consequences we might

be facing if the obesity epidemic continues. "

The Scientist - Magazine of the Life Sciences

http://www.the-scientist.com/news/display/57757/#ixzz12vZz1i92

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