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.