Here's the skinny on fat: One gene controls it all

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SHARON KIRKEY, CanWest News Service; Reuters contributed to this report
Published: 19 hours ago

Scientists have found an anti-fat gene that could be operating in low gear for some people, making them gradually pack on fat, while letting others eat more without ripping a seam in their skinny jeans.

Animals missing a good copy of the gene get fat, are resistant to insulin and have diabetes. But those whose gene is more active are sleek and healthier, even if they eat as much or more.

It's also possible that two people have the same gene, but one person's copy doesn't work as efficiently. That inefficient gene could cost someone to gain an extra pound a year.


Over 30 years, that's 30 pounds,\" said Dr. Jonathan Graff, associate professor of developmental biology and internal medicine at the University of Texas Southwestern Medical Centre in Dallas. \"That's several dress sizes. That's a big difference over time.\"

Graff and his team reported their discovery in this month's issue of Cell Metabolism.

When his team increased the gene's function in genetically engineered mice, the rodents not only weighed less than normal mice, \"they look great metabolically,\" Graff said.

\"Their insulin levels are low, which is what we want to have in humans. Their blood sugars are great. It prevents you from getting diabetes if you turn this (protein) on.

\"They're good-looking, curly haired, lean. And they eat more,\" Graff said.

\"My wife hates this little mouse. It's like a supermodel mouse, she says.\"

So far, the work has been done only in fruit flies, worms and mice, but Graff says the ancient gene exists in humans, too, where he says it likely acts as a kind of volume control that can turn fat storage up or down.

\"If you could find a drug that turns the function of this guy up a little bit, it might be a tremendously useful tool for obesity, diabetes and all those negative consequences we get from those conditions.\"

Scientists have called the gene Adipose, or adp, which actually means fat. It was discovered in the 1950s by scientist Winifred Doane, who thought parts of the world marked by repetitive cycles of feast and famine might be prone to select organisms that are highly efficient at fat storage so that when there's limited food they can handle the fast.

Doane discovered fat flies in Nigeria that carried a mutation in their adp gene.

Doane, now a professor emeritus of zoology at Arizona State University, stressed the flies by starving them and putting them in a desiccator to simulate extreme conditions. Those that lacked a working copy of the adp gene survived, despite starvation and dry conditions.

The discovery was largely forgotten, until Graff's team stumbled upon the same gene while working with worms, looking for what separated the fat from the skinny. (Graff says worms and flies are often used as models of human health and disease.)

When Graff's team turned down the function of the adp gene, the worms got fat. So did a strain of mutant flies they produced that were similar to those found by Doane.

\"It was always my dream that the drosophila (fruit fly) adipose gene would turn out to be a model for controlling obesity and Type 2 diabetes. It looks like it is starting in that direction now,\" Doane said in a telephone interview.

Graff's research showed flies \"with the most fat didn't fly very well and didn't move as fast. What this says is that in times of famine, when your goal is to maintain your ability to survive, you want to have very little of this (gene) activity because it allows you to store a lot of fat and handle starvation.

\"But when times are good, you want to have a lot of this because you're not so worried about nutrition because you have access to food.\"

Today, in Western countries, it's \"all feast and no famine, so that fat builds and builds,\" Graff said. \"You have to think about this in the wild, not when you can go shopping at the grocery store and get all the potato chips you want.\"


The researchers thought the gene might just change how people eat. \"But when they turned up the protein in fat cells, the flies got 'super skinny.' \"

They did the same thing in mice. \"Lo and behold, what happens - the mice are skinny.\" They have very low levels of fat, about one-third the normal. \"And they seemed to eat more than wild mice.\"

Almost 2 billion people worldwide, including 14 million Canadians, are overweight or obese.

Ottawa researchers who sequenced the gene in 400 extremely obese people and 400 very lean people found no evidence that a deficiency increased the likelihood of humans being fat.

However, Dr. Ruth McPherson, professor of medicine at the University of Ottawa Heart Institute, acknowledged there could be a link to preventing people from gaining weight in the first place.

\"It still may be a gene of interest,\" she said, adding: \"The question is, is this a gene we can up-regulate by pharmacological means (drugs) to protect against obesity?\"

Graff and other experts say one place to start looking for humans who have mutant versions of the gene would be Pima Indians from the southwestern United States and Australian aborigines, both of whom have high rates of Type 2 diabetes and obesity when they begin living Western lifestyles.

\"Even if people don't have abnormalities in this gene, if you had a drug that could work on this, you could treat people,\" Graff said.