http://news.yahoo.com/s/nm/20090319..._obesity_gene_1

Researchers find gene that turns carbs into fat

CHICAGO (Reuters) – U.S. researchers have found a gene responsible for turning a plate of pasta into fat, offering new clues about how the body metabolizes carbohydrates and how they contribute to obesity.

The gene, called DNA-PK, appears to regulate the process in the liver that turns carbohydrates into fat, the University of California, Berkeley team reported on Thursday in the journal Cell.

"We hope that this research will one day help people eat bread, pasta and rice and not worry about getting fat," Roger Wong, a graduate student who worked on the study, said in a statement.

When they bred mice with a disabled version of this gene, the mice stayed slim even when fed the equivalent of an all-you-can-eat pasta buffet.

"The DNA-PK disabled mice were leaner and had 40 percent less body fat compared with a control group of normal mice because of their deficiency in turning carbs into fat," Wong said.

He said the mice who lacked this gene did not get fat when they ate high-carb food and they had lower levels of blood cholesterol, which can reduce the risk of heart disease.

Since humans have the same gene, the team thinks it may serve as a potential target for drugs to prevent obesity.

A Role of DNA-PK for the Metabolic Gene Regulation in Response to Insulin

Roger H.F. Wong1,2,Inhwan Chang1,Carolyn S.S. Hudak1,Suzanne Hyun1,Hiu-Yee Kwan1andHei Sook Sul1,2,Go To Corresponding Author,

1 Department of Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
2 Comparative Biochemistry Program, University of California, Berkeley, Berkeley, CA 94720, USA
Corresponding author


Summary

Fatty acid synthase (FAS) is a central enzyme in lipogenesis and transcriptionally activated in response to feeding and insulin signaling. The transcription factor USF is required for the activation of FAS transcription, and we show here that USF phosphorylation by DNA-PK, which is dephosphorylated by PP1 in response to feeding, triggers a switch-like mechanism. Under fasting conditions, USF-1 is deacetylated by HDAC9, causing promoter inactivation. In contrast, feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. DNA break/repair components associated with USF induce transient DNA breaks during FAS activation. In DNA-PK-deficient SCID mice, feeding-induced USF-1 phosphorylation/acetylation, DNA breaks, and FAS activation leading to lipogenesis are impaired, resulting in decreased triglyceride levels. Our study demonstrates that a kinase central to the DNA damage response mediates metabolic gene activation.

http://www.cell.com/abstract/S0092-8674(09)00003-8

What I find most interesting about this is that they refer to carbs turning into fat as if it were common knowledge.

It is common knowledge if you're a biochemist--it's just that this knowledge has not permeated nutritional advice given to laypeople. Basically what Taubes did was review the scientific literature and gather it together. He didn't do anything new, he just put together what had already been done into a coherent picture.

--Melissa

What if this causes people, who live a bit longer than mice, to be unable to gain weight. Being too thin is not good either.

Turning the switch constantly off doesn't seem like a good plan.

How low? Will we die of cancer or suicide from the depression? Both cancer and suicides are linked with low cholesterol levels. Probably Alzheimers too.

Why can't they just tell people not to eat carbohydrates instead of acting as if whole wheat bread/pasta/whatever is the answer to everlasting life/health...

I think my switch is broke! Even when I eat very very low carb, and therefore (theoretically) my insulin is low, I lose very very slowly.....

As I read the abstract, the gene will turn off and on depending upon the fasting state.

It sounds like an autoregulation mechanism - so you don't get so thin that you disappear.

I never understood this concept of "turning on/off a gene". I thought a gene was a basic building block which was replicated in every part of my body. When I think of a gene in my body, I think of identical elements all sitting at a particular place on their respective gazillion chromosones.

How does medicine/chemistry effect a change in these gazillion elements at every location in my body, and once changed, is the change permanent, and does the changed genetic information get passed to my offspring?

Just asking.

Great, let's just alter our bodies (nature) so that we can gorge on foods that aren't supposed to be good for us... wonderful.

This is the difference between genetics and epigenetics, which is a relatively new field in which a lot of research is going on right now. Most of us who lerned biology more than 10 years ago would not have learned about epigenetics in school. Epigenetics has revealed that our biology is considerably more complex than one gene = one protein.

Every cell in your body does have a complete copy of your genome, but it only utilizes certain genes if it's a skin cell, others if it's a brain cell, etc. Epigenetics determines which genes are turned on and off and when this happens, how long it happens, etc. Turning on a gene is called gene expression. Genes that are not expressed cannot be transcribed and function--they just lay dormant basically.

I have seen some research showing that epigenetics can explain a lot of what is unexplained solely from the genome. For instance, they have shown that mice that are exposed to stress early in life have elevated stress hormones not only at that time, but they remain elevated for most of their lives. These changes can be passed to future generations of cells. Some changes may even be passed on to offspring. This may explain why a mother with insulin resistance gives birth to children who are far more likely to get diabetes than the children of a healthy mother.

Wikipedia has a pretty good overview of this and can probably explain it better than I can.

Epigenetics Wiki

Hope that helps.

--Melissa

Thank you. Much clearer now.

I always like to refer people to this wonderful Nova episode on epigenetics. It's really terrific.
http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html

Lovely, I had a stressful childhood and a couple of stressful jobs. So, either I'm screwed or I need to do some feedback meditation

I'll have to check that out over the weekend. I don't work in that field anymore but I still find it fascinating. Thanks for the link Nancy.

--Melissa

So, if the liver is prevented from turning the glucose into fat, what happens to the excess glucose? Does it remain in the blood so that the person has really high blood glucose?