Genetics and Weight

I was going through some of my older files and came across an article from MSNBC from a few years back on genetics and weight. It's pretty interesting stuff. PJ

Scientists have learned that while willpower is important, much of what, when and how much we eat is dependent on our genes.

MARY BETH Syrnick had always had trouble with her weight, but when the scales tipped over 175 pounds the 4-foot-8-inch Philadelphia woman got scared. Syrnick, 54, knew there was a history of stroke and high blood pressure in her family and arthritis was already making it difficult for her to walk. Many times Syrnick had unsuccessfully tried to shed the pounds on her own, but to no avail.

Eventually, she went to a weight-loss clinic where doctors prescribed a low-calorie diet, exercise and the weight-loss drug, Meridia. Two years later, Syrnick has lost 53 pounds and, in a dieting success story, has kept most of it off.

Although her story has a happy ending, it wasn't long ago that doctors used to wag their fingers at pudgy patients like Syrnick. "You just need to be strong and resist those Twinkies," they'd say.
But these days, experts concede that shedding pounds is a lot more complicated than that.
Instead of telling patients to tough it out, weight-loss doctors are increasingly advising their most obese patients to undergo stomach shrinking surgeries. And for those who are overweight but not obese, there is the promise of drugs that will make shedding pounds a lot less difficult.

THE ROLE OF GENETICS

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.

THE THRIFTY GENE HYPOTHESIS'

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.

DNA ALSO AFFECTS WORKOUTS

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."

THE FUTURE OF WEIGHT LOSS

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 at the University of Pennsylvania School of Medicine in Philadelphia.

Wadden is one of the weight-control experts who's changed his mind on surgery. "I used to think it was barbaric," he says. "Now I think it's underutilized. If you're extremely overweight, you should explore it." For those like Syrnick, who are overweight but not morbidly obese, the only options available now are calorie counting, exercise and the current generation of medications that make it a little easier to pass up that extra slice of cake.