Can We Blame Our Parents If We Are Overweight?

If you are overweight, the problem isn't necessarily just your diet, but, in fact, also has something to do with your genetics. But the genes that make a difference in obesity may have been turned on or turned off, and knowing what can turn a gene on or off can actually make a noticeably big difference in your efforts to control your weight.

What do you need to know about how genes can affect your weight?

Fat Mouse, Skinny Mouse

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

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

The difference between the mice wasn't in their genes. Their genes were, in fact, completely identical. So what could it be that made the mice so different? Did Dr. Jirtle perhaps put some of his mice on the Southbeach Diet and feed the other mice some burgers and fries? Did the skinny mice maybe 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? What really happened?

Fat Genes Permanently "Switched Off"

The reason that some of the mice in this experiment 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 agouti 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 this concept, was a little like having computer hardware without the computer software. While the obesity gene was still present in the skinny mice, it couldn't "run" anymore. 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 some factors that could potentially turn the agouti gene back on.

Environmental toxins, it turns out, could actually 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 all of their descendants. The right nutrition, however, could help switch the gene off.

Is There a Way to Switch Off Obesity Genes in Humans?

Human beings, of course, don't carry any genes that will double their body weight and conveniently give them yellow furry coats so that doctors can quickly identify what the problem is. But the discovery of the agouti gene in mice has led researchers to look for ways to reprogram genes for obesity in people as well.

Genetic researchers have identified hundreds of such genes that can be shut down by methylation, the attachment of a methyl group to the molecules that make up a gene. Sometimes a gene can be "strangled" by a chemical group which is known as a histone, which attaches itself to the protein around which the DNA that programs a gene is coiled. And just as genes related to obesity can be switched off in mice, it is also possible for them to be switched off in humans, or not.

The "Fat Dads" Theory of Obesity

Colleagues of Dr. Jirtle at Duke University recently proposed a "fat dads" theory of obesity. When scientists analyzed samples of blood taken from the umbilical cord after births of 79 babies born at Duke University Hospital, the scientists found that children born to heavier fathers tended to have less methylation of a gene called IGF2, which codes the production of a hormone called insulin like growth factor 2.  This hormone stimulates growth of the fetus during pregnancy, but it also has subtle effects throughout life.

IGF2 seems to increase the intensity of fear responses, such as the fear of going without food. It is produced in excess in certain kinds of hypoglycemia, which drives appetite for sweets. The activation of the gene is also associated with a number of different kinds of cancer.

It appears that dads who overeat before participating in the conception of the child contribute "undermethylated" IGF2, an IGF2 gene that may be overactive in their children. Exactly how the overactive gene will affect the health of children born to overweight fathers remains to be seen, but it appears that fathers as well as mothers need to eat healthy for the future health of their children.

The "Fat Moms" Theory of Obesity

Among the babies born to mothers who had not yet had the gastric bypass, 34% were diagnosed as having fetal macrosomia, excessive birth weight. Among the babies born to mothers who had the weight loss surgery before they got pregnant, only 8% were diagnosed as having excessive birth weight.

In a follow-up study, the percentage of children who were severely obese was 70% lower if their formerly obese mothers had had the weight loss surgery before becoming pregnant. This suggests that there is some gene that causes obesity that can be switched off if mothers lose severely excessive weight before they become pregnant, that weight loss can reprogram genes for future generations.

Overeating Isn't the Only Activator of Obesity Genes

It isn't just overeating, however, that may be the culprit in activating obesity genes. Methylation, the process of flipping an "off switch" in some obesity genes, is less likely when people are exposed to benzene, lead, and DDT. It's possible that if one or both of your parents had exposure to these toxins, you will be more likely to be overweight even if you aren't exposed to the chemicals. And the problem may be especially severe if your parents, or even your grandparents, was exposed to drinking water that contained large amounts of arsenic.

There are two things you can do if you have inherited genes for controlling obesity that were deactivated by something your parents did or your parents ate or drank: Eat less, and exercise more. Overeating and toxic exposures may deactivate the genes that protect you from getting fat, but your own diet and exercise efforts can reactivate them again, for both you and your own children.