Rat dad's diet affects pups

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

By | October 20, 2010

A father's diet can directly affect his daughter's health, according to a study in rats published today (October 20) in Nature.

Obese mouse, ornl.gov

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 Michael 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," Tracy 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 Morris, 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 Morris. Together with Sheau-Fang Ng, a pediatric endocrinologist in the lab intrigued by obese families she regularly witnessed in the clinic, Morris 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, Morris told The Scientist.

Pancreatic islet
Courtesy of Ka-Yee Wong, Sheau-Fang Ng, and
Margaret Morris

Presumably, the effects of a high-fat diet -- most likely epigenetic changes such as DNA methylation or histone modification, Morris 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 Morris. 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 Morris. "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."

S.F. Ng, et al., "Chronic high-fat diet in fathers programs B-cell dysfunction in female rat offspring," Nature, 467:963-7, 2010.


Avatar of: Mike Waldrep

Mike Waldrep

Posts: 155

October 20, 2010

Avatar of: amy luper

amy luper

Posts: 1

October 20, 2010

What were the rats fed? Was is it all processed foods? \n\nDid you study natural fats that rats eat in the wild or our backyards versus processed grains and sugary carbohydrate calories? \n\nI think it is important to state what kind of fats/calories cause the rats to be obese. \n\nI think that is one of the problems in the western world. We were told that fats were bad for us. So now everyone eats a high processed carbohydrate diet. They are scared of real food (eggs, butter, meat). They eat lots of salads, though... But getting fatter.\n\nI lived in Lithuania for 4 years (1995-1999). Everyone ate smoked lard on sourdough bread, lots of butter, cream, Kefir, and animal fats. Eggs from the village, and raw whole milk whenever they could get some. Lots of cabbage and whatever was in season. Always something fermented - sauerkraut, kefir, kvass.... No processed foods really - too expensive. The women were beautiful - glowing skin and shiny hair. Only a few OLD ladies were fat, but no one else!!!! They stared at the fat Americans, and asked us how that happened. I taught in a local highschool - the teens were generally radiant with clear skin.\n\nWe visited 8 years later. Now big grocery chains and fast food have moved in, people snack on bags of junk food... teens have acne, dull hair, seem depressed. Where are the beautiful women???? Maybe they moved to London? \n\nThe entire country has put on 20-30 pounds. My once healthy host family has a number of health issues with this weight gain. They are lethargic and feel bad all the time, diabetes, high blood pressure, heart attacks. They complain of allergies.\n\nThey eat low fat/skim milk products, canola oil, white processed breads, packaged foods (with long ingredient lists), pasta... They snack and eat more sugary things. They told us that the lard will make us fat... but look at them now. They don't eat it, and they are fat and sick!!!! They look like our family in Oklahoma. \n\nThey had been eating a traditional diet for generations - they have only changed their eating in the last 10 years.

October 20, 2010

amy luper,\nhow right you are!\nIn Sweden it has taken 30 years to reach the population obesity and diabetes we have, in the Baltic states it's taken less than 10 years to achieve the same obesity as in the rest of Europe.\nAnd our national authorities must have blinkers or even worse tunnel vision/mind as they try to spread the green Keyhole symbol.\n\nWe all know that protein, fat, vitamins amn minerals are essential. They are found in meat, fish, eggs and fat in enough amountes. Vegetables have one to three \nCarbohydrates lack essentiality, need a very sophisticated system including hormones like insulin to survive the toxic carbohydrates. 40 g carbs intravasally and you die.\nCarbs increase glucose in the blood, high glucose releases insulin that inhibit lipolysis, converts carbohydrates to fat, makes you hungry again prematurely as part of the carbs are stored away as fat and the cells start starving craving more carbs to be converted to to fat.\nAll according to the old fashioned honest physiology, biochemistry and hormonology.\nSo skip the carbs and revive yourself!
Avatar of: Richard Patrock

Richard Patrock

Posts: 52

October 21, 2010

Perhaps Lamark should have looked at fat rats instead of long neck giraffes.
Avatar of: anonymous poster

anonymous poster

Posts: 3

October 22, 2010

This paper is wrong and will probably be retracted by Nature.\n\nThe impairment of glucose metabolism that the authors report in this study is ridiculously small (look at Fig. 2). Moreover, their data is based almost entirely on glucose tolerance tests, which are difficult/impossible to use to reliably measure such small differences.\n\nTo understand the mechanism of this "dysfunction", the authors performed microarray analysis from the pancreas of affected and unaffected progeny, and reported a table of genes that were differentially expressed in the two cohorts. Incredibly, the single largest gene expression difference in this table was 1.7-fold, and many of the changes were 1.1-fold. Changes of this magnitude are just microarray noise. These differences couldn't be validated even if the authors tried (and the authors didn't try, as none of the reported gene expression changes were shown to be functionally relevant.)\n\nThis is embarrassing for Nature. The reviewers who handled this paper should be barred from the future practice of science.
Avatar of: anonymous poster

anonymous poster

Posts: 5

October 26, 2010

How is it possible that this study was published in Nature? What is going on? Big claims no supported by the data, that is what you need to get a Nature paper? Nobody realized the magnitude of the reported changes (metabolism and microarrays)? What is the true story behind this publication? Someone from The Scientist, please, read the paper, ask Nature editors for a clarification, and write an article...I think that the scientific community deserves an explanation. This is outrageous.\n\n

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