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At some level we all know that if we're overweight, at some point we ate too much. But some recent findings of genetic research suggest that when we're overweight, what our parents and grandparents ate before we were conceived makes a difference, too.

If you are overweight, the problem isn't just your diet, it is also your genetics. But the genes that make a difference in obesity may have been turned on or turned off, and knowing what turns a gene on or off can make a huge difference in your efforts to control your weight.

Fat Mouse, Skinny Mouse

Geneticist Dr. Randy Jirtle recently retired from Duke University after a long and fruitful career studying the ways genes act in the real world. Dr. Jirtle is a renowned expert in the study of epigenetics, how encounters with the environment switch off and switch on genes, creating an epigenome of activated DNA that really determines how our bodies work. One of Dr. Jirtle's more interesting experiments involved studies of the agouti gene that sometimes determines obesity--and sometimes does not.

Jirtle kept colonies of genetically identical mice, each mouse carrying a copy of a gene known as the agouti gene. Some of the genetically identical mice had brown coats and weighed about 30 grams (about an ounce), and had the capacity to scamper around their cages, while others of the genetically identical mice had yellow coats and weighed about 60 grams, twice as much, and were not capable of doing very much other than lounging around in their cages all day waiting for the next feeding of mouse chow.

The difference between the mice wasn't in their genes. Their genes were identical. So what could it be? Did Dr. Jirtle put some of his mice on the Southbeach Diet and feed the others burgers and fries? Did the skinny mice spend their day running on a wheel to generate electricity to keep the lights in the lab on? Did the fat mice spend too much time watching the Food Network?

Fat Genes Permanently "Switched Off"

The reason some mice were thin and healthy and others were fat and sick, Dr. Jirtle discovered, was that in the skinny mice, the agouti gene was permanently switched off. On a molecular level, a chemical marker known as a methyl group (-CH3) had attached to the gene, so that it no longer coded the proteins that made the enzymes that led to obesity.

The deactivation of the agouti gene, Jirtle was among the first to explain, was a little like having computer hardware without computer software. The obesity gene was present, but it couldn't "run." And once the obesity gene had been switched off in a mother mouse, the gene was also switched off in its offspring, although there were factors that could turn the gene back on.

Environmental toxins, it turns out, could switch on the obesity gene. And when the obesity gene was switched on in a mother or father of a generation of mice, it stayed switched on in their descendants. The right nutrition, however, could switch the gene off.

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