STUDY: Latest research suggests DNA even more to blame for weight

JOURNAL: Howard Hughes Medical Institute at The Rockefeller University in New York City

AUTHORS: Dr. Jeffrey Friedman

ABSTRACT: Despite all the public service announcements telling people how unhealthy it is to be fat, Americans just keep larding on the pounds. Studies have shown that as many as 60 percent of the U.S. population is overweight, while almost 30 percent is classified as obese. Some say the fast-food industry is to blame while others fault super-sized meal portions. But is it just a problem of unhealthy lifestyles or is there something else going on deep down in our cells?

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COMMENTARY: Why the sudden change in weight-loss philosophy? It’s simple. Scientists have learned that while willpower is important, much of what, when and how much we eat is dependent on our genes. In addition, the urge to exercise may also be related to the DNA we inherit.

When it comes to losing weight, we’re fighting against a body regulatory system that has evolved over hundreds of thousands of years to keep us functioning no matter how sparse food becomes. And, scientists have been learning, this genetic influence is stronger in some people than others.

As a prime example of the role of genetics, researchers point to two groups of Pima Indians, one living in Arizona and the other in Mexico’s Sierra Madre Mountains. The Pimas in Arizona have long been known for high rates of obesity, diabetes (almost 50 percent suffer from this disease) and high cholesterol.

The Pimas in Mexico, where food is more sparse and manual labor more common, tend to be lean and have a much lower rate of diabetes than those in Arizona. But despite their healthier lifestyles, the Mexican Pimas still have higher rates of obesity and diabetes than the general population, a finding that leads researchers to point to genes as the culprit.

After studying groups like the Pimas, scientists have developed a theory known as “The Thrifty Gene Hypothesis.” This idea suggests that some of us are born with the Honda of metabolisms — we can go a long way with little fuel.

Other, more fortunate people — fortunate, that is, in times of plenty — have metabolisms that more closely resemble gas-guzzling SUVs. They burn fuel fast leaving bodies slim.

In 1994, when researchers discovered the chemical compound leptin, they thought they had come up with a cure for people with thrifty genes. Leptin is released by fat cells and the larger fat cells get, the more leptin they release.

Normally, when the brain gets a surge of leptin, it concludes that the body has a safe store of fat and sends out a message to dampen appetite.

But, much to their dismay, when scientists tried giving overweight people more leptin to see if it would kill appetite and cause weight loss, the experiments failed.

Most obese people already have high levels of leptin,” explains Dr. Jeffrey Friedman, an investigator with the Howard Hughes Medical Institute at The Rockefeller University in New York City. “But they seem to be insensitive to it.”

Friedman suspected that there might be a way to bypass leptin by looking at enzymes the hormone regulates. Last summer, he and his colleagues found an enzyme related to weight control called SCD-1 and studied the effects of the enzyme in mice genetically engineered to be deficient in it. These mice tended to stay thin, even though they ate more than normal mice, because they had faster metabolisms.

Apparently, the body needs SCD-1 in order to store fat and, without the enzyme, most fat is burned instead of being stashed away.

Another factor in determining whether someone will be heavy or not is the amount time they spend working out. But new research suggests that whether one chooses to become a couch potato may also be the result of their DNA.

Researchers looking at a gene labeled Nh1h2 found that mutations of the gene impacted the impulse to exercise. Mice with certain mutations of Nh1h2 tended to be lethargic.

“Basically, if you put a normal mouse in a cage with an exercise wheel, he’ll run,” explains Deborah Good, an assistant professor of vertebrate molecular genetics at the University of Massachusetts in Amherst.

“But the mutant ones, if you put them in a cage with a wheel, they’re not interested in running,” says Good. “There’s nothing physically wrong with them. They did as well or better in tests with forced exercise. They just don’t want to run.”

While genes may ultimately explain why some of us tend to be pudgy and others stay slim, research into one’s DNA won’t offer any practical help with weight loss for the time being, experts say.

“At present, we’re at least five years away from having any therapeutic applications based on genes,” says Thomas Wadden, director of the Weight and Eating Disorders Program.