3

votes

Epigentic effect of paternal obesity on progeny in Nature

Answered on August 19, 2014
Created October 25, 2010 at 12:03 PM

I became very interested in the role of epigenetics after listening to a podcast about the emerging field. I found it to be a fascinating expansion of the mechanics of natural selection, albeit one I am not intimately familiar with.

The methylation of DNA to control gene expression has been well established and understood for years but the transmission of methylated DNA was not something researchers had considered. Anyone interested might want to check out the following study just published in Nature: http://www.nature.com/news/2010/101020/full/news.2010.553.html

I have not seen the entire study and it was done using Mice and a "high fat" diet but none the less I suspect there is an indication here that an obese parent could be setting up their progeny for metabolic derangement. In fact a good deal of the people reading this are likely the RESULT of this effect.

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 08:16 PM

Take this with a grain of salt, but to my knowledge, it's not well known. I can say that its difficult or impossible to maintain biologically significant concentrations of the epigenetic active compounds when consuming many of those foods/supplements you listed, but I don't believe low-dose long term exposure has been clinically explored. Some of the methyl donors have been examined in terms of disease treatment/prevention for specific ailments, but I doubt if anyone has examined general effects on overall health without targeting a disease.

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on October 25, 2010
at 06:25 PM

Everything I mentioned above is a known, or suspected, inhibitor of either methyltransferase or HDAC. I am interested in the long-term effect of such dietary measures and I wonder how such a "reprogramming" syncs with consumption of dietary methyl-donors, like folate, B-6, choline, and methionine.

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on October 25, 2010
at 06:24 PM

Everything I mentioned above is a known, or suspected, inhibitor of either methyltransferase or HDAC. I am interested in affecting these changes gradually over years with diet and some supplements. I wonder how such a "reprogramming" syncs with dietary methyl-donors, like folate, B-6, choline, and methionine.

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 06:18 PM

You can absolutely push your epigenetic cards in a better direction with proper diet and lifestyle. It's not just about DNA methylation, though--you can change entire broad swaths of your cellular protein with those foods, just as you can alter histone modification status that will change the relative expression at certain genes. Resveratrol and EGCG in green tea are good examples of this, as they both activate sirtuin protein deacetylases. Incidentally, the sirtuins are the proteins that have been associated with enhanced lifespan in some lower model organisms.

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 06:10 PM

It's really a PI-dependent field; most of my department focuses on metabolic processes in cancer and we happen to be the epigenetics guys. Lots of labs are moving towards using epigenetic phenomena to describe gene expression patterns, and there's probably someone working in the field in programs that you might be applying to. Some names to look into for some good background would be David Allis, Tony Kouzarides, and Randy Jirtle--all of these guys are huge names in epigenetics that have great literature to their names and would be good places to start. Hope that helps!

A0b8c4cc369f93ee987ce15b1bf323fe

on October 25, 2010
at 05:41 PM

TC, what type of graduate program are you in? I have been interested in genomics and more recently epigenetics, and I'm looking to gain more exposure into this field through graduate studies...

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 02:18 PM

You're absolutely right; I'm a little bit prone to overstatement sometimes. One of the critical things about epigenetics is its inherent plasticity. Your parents might give you a particular epigenetic canvas to work with, but you get to paint it with your health/eating/environment choices throughout your life. While the canvas is non-negligible in the equation, the picture you get is still totally up to you and your habits. This assumes that you've maintained the epigenetic capacity for normal development, which unfortunately is not always the case.

77732bf6bf2b8a360f523ef87c3b7523

(6157)

on October 25, 2010
at 01:25 PM

*...we'll be forced to accept that you aren't really what you eat--it's more like you are what your parents and grandparents ate.* Isn't this overstating the case a little? What I eat has a huge impact on my health outcomes, even if the range of those health outcomes is somewhat limited by genetic and epigenetic factors.

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2 Answers

3
3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 12:50 PM

Nice post! I actually am a graduate student studying epigenetic phenomena, and specifically how metabolism affects epigenetic regulation of gene expression, so it's nice to see this community pick up on some of those topics.

I will say that it's actually been demonstrated previously that the parental involvement in the transmission of epigenetic phenomena is a significant process, and could point you towards a base of other interesting literature if you're interested in learning more. Along similar lines to what you're talking about, Randy Jirtle's laboratory established that you can basically titrate the coat color of mouse pups based upon how much folic acid you give the mothers during pregnancy, in a way that correlated strongly with the degree of DNA methylation at the agouti (yellow) locus in the mouse genome. Epigenetic phenomena are also largely the reason that we want pregnant mothers to take folate supplements, because folate is critical for one-carbon metabolism that leads to methyltransferase reactions such as those that result in DNA methylation. What makes the study that you present interesting is that it doesn't necessarily involve maternal nutrition status during pregnancy, which is where most of the findings have been made to date.

I think that as more research becomes available, the more we'll be forced to accept that you aren't really what you eat--it's more like you are what your parents and grandparents ate. So there's another reason to be healthy: do it for the kids you might want to have someday!

A0b8c4cc369f93ee987ce15b1bf323fe

on October 25, 2010
at 05:41 PM

TC, what type of graduate program are you in? I have been interested in genomics and more recently epigenetics, and I'm looking to gain more exposure into this field through graduate studies...

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 02:18 PM

You're absolutely right; I'm a little bit prone to overstatement sometimes. One of the critical things about epigenetics is its inherent plasticity. Your parents might give you a particular epigenetic canvas to work with, but you get to paint it with your health/eating/environment choices throughout your life. While the canvas is non-negligible in the equation, the picture you get is still totally up to you and your habits. This assumes that you've maintained the epigenetic capacity for normal development, which unfortunately is not always the case.

77732bf6bf2b8a360f523ef87c3b7523

(6157)

on October 25, 2010
at 01:25 PM

*...we'll be forced to accept that you aren't really what you eat--it's more like you are what your parents and grandparents ate.* Isn't this overstating the case a little? What I eat has a huge impact on my health outcomes, even if the range of those health outcomes is somewhat limited by genetic and epigenetic factors.

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 06:10 PM

It's really a PI-dependent field; most of my department focuses on metabolic processes in cancer and we happen to be the epigenetics guys. Lots of labs are moving towards using epigenetic phenomena to describe gene expression patterns, and there's probably someone working in the field in programs that you might be applying to. Some names to look into for some good background would be David Allis, Tony Kouzarides, and Randy Jirtle--all of these guys are huge names in epigenetics that have great literature to their names and would be good places to start. Hope that helps!

0
4781cf8ae1bfcb558dfb056af17bea94

(4359)

on October 25, 2010
at 04:40 PM

And can you fix the problem by de-methylating (presumably in conjunction with a proper diet)? Green tea, soy, turmeric, cruciferous vegetables, garlic, butter, kombucha, CLA, melatonin, and resveratrol are all reasonably likely to cause some degree of de-meythlation (edit: or histone modification) (without resorting to the harder stuff)...

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 08:16 PM

Take this with a grain of salt, but to my knowledge, it's not well known. I can say that its difficult or impossible to maintain biologically significant concentrations of the epigenetic active compounds when consuming many of those foods/supplements you listed, but I don't believe low-dose long term exposure has been clinically explored. Some of the methyl donors have been examined in terms of disease treatment/prevention for specific ailments, but I doubt if anyone has examined general effects on overall health without targeting a disease.

3bc67f572ead57591a295f4913fa5991

(315)

on October 25, 2010
at 06:18 PM

You can absolutely push your epigenetic cards in a better direction with proper diet and lifestyle. It's not just about DNA methylation, though--you can change entire broad swaths of your cellular protein with those foods, just as you can alter histone modification status that will change the relative expression at certain genes. Resveratrol and EGCG in green tea are good examples of this, as they both activate sirtuin protein deacetylases. Incidentally, the sirtuins are the proteins that have been associated with enhanced lifespan in some lower model organisms.

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on October 25, 2010
at 06:25 PM

Everything I mentioned above is a known, or suspected, inhibitor of either methyltransferase or HDAC. I am interested in the long-term effect of such dietary measures and I wonder how such a "reprogramming" syncs with consumption of dietary methyl-donors, like folate, B-6, choline, and methionine.

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on October 25, 2010
at 06:24 PM

Everything I mentioned above is a known, or suspected, inhibitor of either methyltransferase or HDAC. I am interested in affecting these changes gradually over years with diet and some supplements. I wonder how such a "reprogramming" syncs with dietary methyl-donors, like folate, B-6, choline, and methionine.

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