UF helping unlock a way to prevent weight gain?


Published: Tuesday, January 8, 2013 at 4:30 p.m.
Last Modified: Tuesday, January 8, 2013 at 4:30 p.m.

A pill for permanent weight loss?

Not quite, but scientists are on the trail of potentially reversing obesity, from deep inside our own cells.

A recent study published in Nature Medicine discussed a "master protein" called TRIP-Br2 that is linked obesity. Deleting the protein in mice made them leaner -- even if they ate high-fat diets. Although studies still need to be done in humans, scientists are excited that they have unveiled a key biological mechanism underlying a problem that just keeps getting bigger: Two-thirds of U.S. adults are overweight or obese, as are one-third of children and teens.

"The presence of the gene and the protein it encodes is permissive to getting fat. When it's not there, it's like the dam opening up" to weight loss, said Stephen Hsu, one of the study's authors and a principal investigator with the University of Florida Sid Martin Biotechnology Development Institute.

Hsu explained that since TRIP-Br2 represses certain proteins, knocking it out releases those proteins' functions, which results in increasing metabolism as well as the production of ATP, or the thermal energy used in metabolism. The proteins also help the body break down fat instead of storing it.

"It combines these three things together in a way that has not been described before," said Dr. Rohit Kulkarni, another author of the study and an associate professor of medicine at Harvard University.

"It's more powerful than drugs that affect only one of the three mechanisms," Kulkarni said.

But Kulkarni added that they are still a few years away from studies in humans. He is especially interested in doing studies on younger people who may be more susceptible to obesity later on.

Hsu added that in terms of drug development, their research lays the groundwork for potential drugs that "pharmacologically mimic a knock-out" of the TRIP-Br2 protein.

"The industry's gotten burnt with anti-obesity drugs, but this is different than reducing appetite. It doesn't rely on human behavior," said Hsu. "You would have a drug that no matter how much you eat, you'll just burn it all off."

The study's findings support this, Hsu continued, since even the mice eating a high-fat diet who'd had the protein knocked out were leaner than those that still had the protein. This was also significant since the mice were older, and aging is linked to a slower metabolism and weight gain.

Hsu said potential drugs that could come out of this research would be especially good for people who are genetically prone to obesity. This research also opens the door to discovering what some of those genes are, he said.

"If we knew what genetic variations are involved, you could actually develop a genetic test, just like the BRCA genetic mutations test for breast cancer."

Meanwhile, Kulkarni cautions against conceiving of a drug as a panacea against the obesity epidemic overall.

"We still have to make sure that a healthy diet and healthy exercise tops the list of priorities," he said. "But we do know that some people, even when they do these things, cannot lose weight."

Clinically, that's very true, according to Dr. Richard Shriner, a psychiatrist at University of Florida who specializes in obesity medicine. Shriner said the obesity epidemic is a "very complex issue" that involves people's problematic relationship to food and at its most extreme, food addiction, which has recently emerged as a serious problem.

"I see hundreds of people who are obese, and you bring up the issue of food addiction, and discover that it is a very real problem," said Shriner. "Their brain lights up the same as a person who has a cocaine addiction."

Foods high in sugar and fat are the most addictive, Shriner added, and not surprisingly, sugar intake has surged 500 percent since the early seventies -- in parallel with the rise in obesity -- mostly because of soda consumption.

Shriner said medications are being developed to stimulate areas of our brain that turn down our desire to eat. Bariatric surgery, which reduces the size of the stomach, is also on the rise.

Shriner said it's important to emphasize the health peril that obesity carries instead of the social stigma.

"If we treat obesity, the rationale is to prevent type 2 diabetes," he said, noting that this message could resonate globally since, "No culture is immune to the obesity epidemic and type 2 diabetes," he said. "The epidemic is spreading like wildfire across the world."

China has one of the world's fastest growing rates of childhood obesity, he added.

Aside from medical interventions, some people believe the government has a role in curbing the obesity epidemic by encouraging healthier eating: a recent poll conducted by the Associated Press-NORC Center for Public Affairs Research found that a third of those surveyed believe the government should be involved in solutions to the problem -- namely by encouraging exercise in schools and making restaurants post calorie content on their menus.

But most people surveyed oppose taxes on junk food and sodas.

According to Shriner, "It's always best to set up things that motivate, not chastise people."

Contact Kristine Crane at 338-3119, or kristine.crane@gvillesun.com.

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