Obesity: NTR 562: Obesity runs in families…but exactly how remains a mystery!

Monday, September 15, 2014

Obesity runs in families…but exactly how remains a mystery!

Of all inherited traits, obesity is one of the strongest. However, despite enormous advances in genetics research over the past two decades, very little progress has been made in untangling exactly how genetic factors work to determine body weight. The magnitude of genetic influence on the current obesity epidemic also remains to be determined.

A recent article in the Nature Outlook Supplement underscores the complexity of the issue and outlines where we currently are in our understanding.

The author, Cassandra Willyard, explains: “Many scientists had first assumed that the heritability of obesity would be explained by common genetic variants. But that hasn’t held true.” The genome-wide association studies (GWAS), from which we’ve obtained most of our information about obesity genetics, have revealed many common variants, but all together these explain less than 5% of the variability that is attributed to genetics. One scientist quoted in the article refers to this as the “dark matter of quantitative genetics”. There is agreement among scientists that up to 70% of body weight variability is due to genetic factors even though no one can yet explain how this works. Three possible answers are provided in the article:

One possibility is that some genetic variants related to obesity have yet to be discovered. Since GWAS can only identify variants common in greater than 5% of the population, less common variants may yet emerge and may demonstrate a more pronounced impact on obesity than the common variants.

Another interesting possibility is that our genes must interact with our environment to be expressed. The GWAS study methods simply can’t account for this complexity yet. One featured study showed that individuals with one common genetic variant were predisposed to eat greater quantities of food and weighed, on average, 6.6 pounds more than those without the variant. Men in this variant group were also shown to have higher levels of the appetite-stimulating hormone ghrelin. The best evidence we have so far though is from a large meta-analysis study which showed that people who carry a common “susceptibility gene” have a higher risk of obesity, but that this risk is much lower in people who are physically active. In this case, a single environmental influence in essence protects individuals from their genetics. What’s suggested is that our current obesigenic environment may exert much more influence on some individuals than others purely based on their individual biology.

Also intriguing is the evidence that gene expression is strongly influenced by the intrauterine environment. The concept of “fetal programming”, as the author puts it “raises the possibility that a mother’s experiences during pregnancy –such as malnutrition – can influence the next generation.” Put another way, lifestyle factors during pregnancy can influence an offspring’s gene expression without altering the genetic code – and may also alter gene expression in the offspring’s offspring. “When a pregnant woman experiences malnutrition or some other environmental stress, three are directly exposed – the mother, the child in her womb and also her grandchildren." This presents one more way obesity can be “passed down” among generations. A father’s exposure and lifestyle habits appear to have some influence as well, though the effect appears not to be as strong or persistent.

Overall, an interesting dynamic in the nature vs. nurture discussion is emerging. We know that as obesity rates have risen in the past 30 years, our environment has changed dramatically, while our genetic code has not. We also know that up to 70% of variation in body weight is attributed to genetics. It seems gene-environment interactions – particularly in utero - may prove to be the missing link. So, while our genetic code has not changed, our genetic expression has and these changes are now being passed down through successive generations.

2 comments:

UnknownSeptember 16, 2014 at 1:05 AM
In recent decades, obesity has reached epidemic proportions in populations whose environments promote physical inactivity and increased consumption of high-calorie foods. However, not all people living in such environments will become obese, nor will all obese people have the same body fat distribution or suffer the same health problems. These differences can be seen in groups of people with the same racial or ethnic background and even within families. Genetic changes in human populations occur too slowly to be responsible for the obesity epidemic. Nevertheless, the variation in how people respond to the same environment suggests that genes do play a role in the development of obesity. Other studies have compared obese and non-obese people for variation in genes that could influence behaviors (such as a drive to overeat, or a tendency to be sedentary) or metabolism (such as a diminished capacity to use dietary fats as fuel, or an increased tendency to store body fat). These studies have identified variants in several genes that may contribute to obesity by increasing hunger and food intake.
The Obesity & Genetics case example can be considered as a perfect example of gene environment interaction .The parents been related (first cousins) passed on the single gene defect to the child. Here as the child suffers hyperphagia due to lack of the hormone leptin, the consumption of food by the child was 6500 calories at one time. Been unable to sense satiety, the exposure the calorie dense foods were very high thus resulting in consuming a big meal every time. Consumption of calorically dense big meals increases calorie intake compared to expenditure resulting in excessive weight gain and obesity.
When incorporated with hormone injections, the child was able to get down to its normal weight. Another factor that could be used for the child was adding physical activity to his everyday routine which may have helped in somewhat taking care of the excessive calorie consumption and would be helpful in showing that environment can be used in bringing positive changes in our life.
Just like malnutrition during pregnancy, other factors like smoking habits, excessive weight gain, high blood sugar levels has life time influence on the infants and future generations. Smoking during pregnancy tends to slow the rate of fetal growth, children of women who smoke during pregnancy are more likely to be obese than the children of women who don’t. In a meta-analysis of 14 studies, maternal smoking during pregnancy was associated with a 50 percent higher risk of childhood obesity. Most of the studies looked at children’s obesity status at ages 3 to 7; one study assessed obesity at age 14, and another tracked the children all the way to young adulthood.
Children of women who gained an “excessive” amount of weight had more than four times the risk of being overweight at age 3, compared with children of women who gained an “inadequate” amount of weight. Even women who gained what was considered at the time to be an “adequate” amount of weight bore children who were nearly four times more likely to be overweight at age 3 than children of women who gained an “inadequate” amount of weight.

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