Fat rat fathers and pre-diabetic daughters

Oct 25 2010 Published by under Physiology/Pharmacology, Uncategorized

You guys, there is SO much science out there. SO MUCH. Grrl and I agree, so much to blog, so little time. Anyway, I found this great paper in the latest Table of Contents for Nature, and went "ooooh, must blog!" And then SciAm beat me to it. No fair, I bet they had it with embargo and all. 🙂

Anyway, this article also appeared in various other places, and it, and articles like it, have received a certain amount of unfortunate attention due to the nature of the coverage. I do not deny that reposting the press release (or repurposing the press release without reading the article) is a bit lazy. On the other hand, I feel like this is not just the fault of main stream media or Lab Spaces. I feel like Dr. Isis said it very well when she stated:

One thing that has become abundantly clear to me in the last 24 hours, however, is that neither scientists nor journalists should rely on the university as a source of information.

She is very right. These press releases are not written by the scientists (often they are barely signed off by the scientists), they are written by the university's PR dept, who knows about as much as anyone else who is not a scientist about what the data actually SAYS. Rather than blaming journalists about what got written about their work, perhaps scientists should first take a look at the press release.

But anyway. Sci's not going to get further into that fray. I hate frays. But I LOVE SCIENCE. And I liked this article. So. Here's the press release, if you want to read it.

And HERE is the paper:

ResearchBlogging.org Ng et al. "Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring". Nature, 2010.

As you might be aware, Americans (and many people in the world) are becoming more obese. This results from a combination of factors like genetics and environment, but HOW these factors combine is still a mystery, and is part of the question this paper is tackling.

We know that obesity in parents drastically affects the potential for obesity in offspring. The association between maternal obesity and obesity in the offspring is the most well-established. But of course, only half your genes are from your mom. You ALSO get half your genes from your DAD, and not only do you get their GENES, you get everything that goes with them.

I'm talking here about epigenetics. We do know that male obesity has bad effects on things like sperm count and sperm swimming in humans. But there's more to it than that. You get half your DNA from your dad, but what you ALSO get is the epigenetics of those genes, which refers to the way they are expressed. Epigenetics refers to inherited changes in gene EXPRESSION. This can happen via several means, but what I'm going to stick with here is DNA methylation.

DNA methylation (which I actually covered just a few posts ago, go figure!) is a process where certain protrains (DNA methyltransferases) add a methyl group to the cytosine of the DNA (The cytosine is the C of the GTAC of DNA bases). When this happens, the DNA which is methylated may become more or less capable of being transcribed (depending on where the methylation happens and how many there are), and thus may be made more or less capable of being translated into proteins.

But here's the kicker. DNA methylation doesn't stop with that cell. It can go through several generations of that cell, too! It persists. And it can persist into your offspring. This is of particular interest when you're looking at things like a male's sperm. A male's sperm turns over (I'm not sure how often, a quick search didn't tell me, but it's apparently more than a week), and thus the production of new sperm can be affected by things in the male's environment. Like, say, your diet.

So the authors of this study wanted to see if a high fat diet in father rats changed the gene expression they passed on to their offspring. Like I said, we KNOW this happens in moms, but it hadn't been looked at in dads. So they fed a bunch of male rats a high fat diet (in some studies they really DO feed them Crisco, but in this study it was a specialty high fat diet for rats). They then mated those rats, and checked out their daughters.

As expected, the male rats fed the high fat diet gained a lot of weight and developed insulin resistance. This means that they were unable to release insulin well enough to combat a sugar load, to get all that sugar inside the cells. The sugar load then remains in the bloodstream, resulting in high blood sugar.

The top row of figures is various measurements of the father rats' weight, and the bottom row shows their increase blood sugar in response to a sugar load, indicating that they were less sensitive and releasing less insulin.

So then they mated those male rats to normal female rats, and looked at the daughters. (They actually ended up looking at the daughters because there were no quick effects that were present in the sons.) The daughter rats had lower birthweight (which has been seen before in humans). Not only that, the daughters showed impaired glucose tolerance, just like their dads.

Here you can see the daughters. When tested with glucose, the daughters had a higher blood glucose and a lower insulin response, showing that they were insulin resistant like their fathers. What I found particularly cool about this is that the daughters were NOT OBESE. They ended up normal body weight on a normal rat diet.

Ok, so fat rat fathers make for pre-diabetic daughters. The question is, HOW does this happen? It turns out that a high fat diet in father rats affects 77 different gene expressions in the daughters. These genes controlled things from insulin resistance and secretion to changes in the shape and size of the beta cell islets in the pancreas (the daughters not only showed reduced insulin, they showed reduced beta cell islet size, which are the cells producing insulin). The genes were changed by changes in DNA methylation at the sites of some of these genes. The high fat diet in the fathers had induced epigenetic changes which they then passed on to their daughters.

Now this sounds really cool, and it IS. It's a very new and interesting look at how environmental things like your diet may not only affect YOU, but affect your kids! But don't panic just yet. This was a small study in rats, and the differences, though there, were not enormous. The daughter rats didn't end up obese on a normal diet. Not only that, they don't know the effects of fat fathers who lose weight, or daughters who eat high fat diets, or the relative effect if your mother is on a LOW fat diet. Sure, fat rat fathers CAN produce pre-diabetic daughters, but that is less than half the story.

Ng, S., Lin, R., Laybutt, D., Barres, R., Owens, J., & Morris, M. (2010). Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring Nature, 467 (7318), 963-966 DOI: 10.1038/nature09491

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