Do these genes make me look fat?

New findings on the genetics of obesity
Obesity is a huge problem in this country (pardon the pun). It is linked to type 2 diabetes, heart disease, metabolic disorders, and hypertension. Obesity is costing the country a fortune in medical costs. And none of this even mentions the associated social stigma. In 1962, 13% of the American public was obese. By 2000, that number had climbed to 31%. 3.8 million Americans weigh over 300 pounds and 400,000 Americans weigh over 400 pounds. Part of the reason obesity is this common is that lots of people are predisposed to becoming obese. This is because of their genes. Of course, back in 1962 folks had pretty much the same genes they do now. What has changed is our lifestyles. We eat more and exercise less. Simple as that. We just need people to eat less and exercise more and the problem will be solved. Why then should we even care about the genes involved? Well, despite an almost constant badgering from friends, family, doctors and the media, the rates for obesity continue to climb. These people are not weak or lazy; they need help in maintaining their correct weight given the new environment humans find themselves in. If we can find the people who need the most help, we might be able to intervene early. Maybe something like special training in diet and exercise could help people who are more likely to be obese. We might also learn new ways to treat obesity. Let's say we find a DNA difference associated with a particular gene. If we find that the gene is involved in obesity, we may be able to design medicines to reverse the gene's effects. In other words, finding a gene might lead to a treatment. So how do you go about finding these DNA differences between obese and non-obese folks? It is not easy. As I said, most DNA differences that lead to obesity are not destiny. Having these genes only means that it is harder to maintain the right weight. This means there will be people who have the genes but are not obese. To complicate things further, there isn't just one gene involved. There are lots of genes involved and different people will have different combinations to explain their obesity. Because there are so many different genes involved, you need a way to look at lots of different genes all at once to find the obesity genes. A few years back this would have been difficult if not impossible. We just didn't have the technology. Now we do. The technology is called microarrays. Microarrays are like thousands of genetic tests done on a single glass slide all at once. Cool, huh? The way you might do an experiment is to collect samples from obese and non-obese people and look at their genes on a microarray. Any changes that happen more often in the obese group are candidates for DNA changes that might lead to obesity. Two new studies use microarray technology to try to figure out the genes involved in obesity. The first study looks at thousands of obese and non-obese people and finds a common DNA change. The second study looks at around 200 people and finds 3 genes that can accurately predict body shape.
A needle in a haystack
The first group studied a large group of families to see if they could find a common DNA difference that might predict obesity. This is even harder than it sounds. People are on average about 99.9% the same. With 6 billion bases, though, that means 6 million differences between you and me. And not the same differences between me and someone else. So there are a lot of differences to look at, most of which have nothing to do with obesity. Add to this that there is more than one gene involved in obesity and we make the problem even worse. Imagine one group of obese people has DNA differences X, Y, and Z that increase their chances for being obese. Another group has A, B, and C. The third group has X, Y, and A. And so on. Even though all of these DNA differences are involved in obesity, none of them would look significant when you looked at everyone. Most obese people wouldn't have the same changes. So you need to get lucky and find one that is shared by a lot of people. And a group of researchers did get lucky. Using microarrays, they looked at around 116,000 DNA differences in 700 people from various families and found one difference that looked significant. Just one. The researchers then tested thousands of other people for this specific change. They found that the DNA change was associated with obesity. But only if both copies of chromosome 2 had the change. Remember, we get one chromosome from mom and one from dad. So to be predisposed to obesity, you need to get this DNA change from both parents. This means that the trait is recessive—both copies need to have the difference to see it. OK, so how does this DNA change make it more likely you'll be obese? Maybe by affecting a nearby gene called INSIG2. We know that if you affect this gene, you get increased triglycerides. And increased triglycerides could lead to increased fat storage. And this would lead to obesity. If it is shown that INSIG2 is involved, then scientists may be able to come up with a way to affect the gene. And maybe help give people a level playing field for obesity. Medicines may not let people eat whatever they want. But maybe these medicines might let people with certain DNA differences eat like other people without becoming obese. That is progress.

More Information

Finding obesity genes is like
well, you know
DNA differences
contribute to obesity
Body shape
Pretty early on it was found that some forms of obesity were worse than others. If you tend to get fat deposits around the waist in the classic beer belly, then you are more likely to suffer from heart disease. Our next group of researchers decided to figure out why people store fat differently. They found three genes that seemed to pretty accurately predict where someone's fat deposits will end up. How did they find these genes? Microarrays. The microarrays they used were a bit different than the one our first group of researchers used. The first group was looking for DNA changes. The second group was looking for differences in how genes are expressed. What does this mean? Genes are simply recipes for making certain proteins. And these proteins are the cell's worker bees. They do most of the work based on instructions from the DNA. Now, having a recipe doesn't give you a meal. You need to read the recipe, collect the ingredients, and follow the instructions. Genes are like this too. If a cell doesn't read a gene, then it doesn't make that gene's protein. It is like not having the gene. So a gene can be on (read by the cell) or off (not read). Like a recipe, a gene can also make more or less protein (sort of like the Bisquick box that has recipes for making different amounts of pancakes). How much protein gets made depends on the exact recipe a person has (their DNA sequence) and/or how much of the ingredients are left. So our second set of researchers wanted to know which genes are turned on in different fat deposits. And to what level. They started out looking in mice. Specifically, the researchers looked at 6200 genes in fat deposits from two different places in the mice. They found around 7 genes that were turned on to different levels in the two fat deposits. They then did further testing and narrowed the genes down to five. Next they moved on to people. In people they found that how much three of these genes were turned on did a remarkable job of predicting where fat would be stored in a person. This is all cool but pretty academic at this point. Yes it is interesting to know why some people are shaped the way they are but can knowing this help them? Maybe, maybe not. Remember, people who tend to store their fat around their waists are at a higher risk for various diseases. Let's say one of these genes is the reason. Then, if we can find a way to affect the gene then we may be able to find a medicine to affect the gene. It is important to note that there is no link here between disease and these genes. These genes may just be a side effect of other genes. But even if that is true, it is a good clue for finding the real culprit genes.
Some body shapes have a
higher risk of heart disease
Genes are like
recipes for proteins