Wow, parents with gastric bypass may pass on benefits to children.
Gastric bypass surgeries would, at first glance, seem to tackle the problems of obesity through simple physics: with a smaller stomach, there's only so much food a person can ingest. Actual results are anything but simple, however. Long before any significant weight loss occurs, patients who have the surgery show a remarkable reversal in many aspects of type-2 diabetes and cardiovascular risk factors. This suggests the body responds physiologically to the altered food intake itself rather than its impact on obesity.
New research shows that the effects may go beyond the patients themselves. A study has been tracking women who have had kids both before and after these surgeries, and it reveals that the children also see changes in how their bodies handle fats and sugars (as well as in markers of cardiovascular health). The researchers have found that the offspring may be benefiting from epigenetic inheritance, in which the parent's surgery influences how the DNA they inherit is interpreted by their cells.
Epigenetics and hunger
Epigenetics has become a rather confusing topic, in part because it has become an umbrella term that covers two very different phenomena. In general, epigenetics describes traits that are maintained without any changes in the underlying DNA sequence. The phenomenon can both occur over the course of a single individual's lifetime and, in rare cases, it can span generations.
Within an individual, the traits that are inherited are passed from cells to their offspring. Early in your development, there's a single tissue that will give rise to both the skin and all nerve cells; the difference comes down to whether a cell sees more or less of a specific signal. Once the decision is made, however, the signal becomes irrelevant—nerve cells lock their decision in place and pass the decision on to their daughter cells when they divide. This occurs through a combination of proteins that shut genes off and lock sections of the chromosome in active or inactive states.
That process may last a lifetime, but it can't pass information on to the next generations. Sperm get rid of most of these proteins, and eggs simply have whatever proteins got them to be an egg. But there is a way for things to be handed down across generations that doesn't involve a change in the sequence of bases in the DNA. Some bases (primarily cytosine) can have an extra carbon atom chemically attached to them. This modification will survive sperm and egg production, and it can be maintained as a cell divides. The change can then alter the activity of nearby genes, affecting how an organism develops or behaves. (Although it's a form of epigenetics, this specific process is called imprinting.)
There is a lot of excitement about epigenetics, partially because some of these changes seem to underlie the transformations involved in cancer. But most of what we're learning does not involve imprinting. There's little solid evidence that imprinting takes place in humans.
One of the exceptions, however, may be diet. During World War II, the occupied Netherlands experienced a severe famine called the Hunger Winter. Women who were pregnant at the time gave birth to children who had an altered physiology, and they were generally shorter than their peers. But those individuals' children also tended to be shorter, on average, a full generation after the famine occurred, which suggests some form of inheritance is involved. Researchers have discovered a form of imprinting is likely to be the culprit.
Gastric bypass and health
As we noted above, gastric bypass surgeries tend to leave the patients healthier than we would expect. Although those patients lose weight over time, they experience other benefits almost immediately: reduced type 2 diabetes, better cardiovascular health, and better regulation of glucose and lipid metabolism. The surprise is that, by comparing children born before and after their mothers had this surgery, researchers found that children see significant benefits as well. The changes include reduced obesity, lowered hypertension, and better regulation of fat metabolism. And these differences continue into adulthood.
Now researchers have gone through and tracked what's going on with imprinting in these same children. They looked at thousands of sites in the genome where chemical modifications of DNA are known to happen and then looked at whether nearby genes showed differences in their activity. Lots of areas of the genome came through one or the other assay, but only three percent of the sites showed both evidence of imprinting and altered gene activity.
The genes nearby are generally what one might expect. Many of them are involved in glucose metabolism, while others are involved in inflammation (a feature of type 2 diabetes) or implicated in vascular disease. A number of these are likely to be false positives, but the evidence still strongly suggests that the imprinting of some could explain how the surgery triggers long-lasting effects in the offspring of the person who had it.
There are some weaknesses to the study. The population involved is quite small, and they are a variety of ages (which may affect the results in various ways). Again, humans have more than 20,000 genes, so the three percent figure still leaves a lot of genes potentially involved—some of these will be important; others will just be random chance.
Still, the paper as a whole makes a compelling case that imprinting could have a significant role in making an acquired characteristic (obesity) a heritable trait. So these surgical obesity interventions may do more than just aid the health of the person who receives one.