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Anti-Fat Protein Keeps Overeating Mice Slim

But experts question its potential for humans

MONDAY, Sept. 18, 2006 (HealthDay News) -- Mice gorging on high-calorie, high-fat diets for two weeks stayed slender, thanks to an "anti-obesity" protein injected into their brains, Italian researchers report.

Eating all you want and never getting fat does seem like a dream come true. And experts cautioned that it might stay a dream -- at least for humans -- for the foreseeable future.

"Whether this translates to humans and whether it translates to humans without tremendous side effects is another story," said Cathy Nonas, director of the obesity and diabetes programs at North General Hospital in New York City, and a spokeswoman for the American Dietetic Association.

The study was published in this week's issue of the Proceedings of the National Academy of Sciences.

According to Nonas, a "wonder drug" that wards off obesity while allowing people to eat all they want has long been the goal of pharmaceutical companies worldwide. So far, most research efforts have focused on agents that "rev up" metabolism to burn off excess calories.

"People have been working on the idea of looking at molecules, peptides, to see whether they could increase energy expenditure without major side effects," Nonas said.

This latest research, led by Alessandro Bartolomucci of the Consiglio Nazionale delle Ricerche, in Rome, focused on a protein byproduct of the Vgf gene, which has long been linked to metabolism.

Bartolomucci's group first identified this protein, a peptide called TLQP-21, in the brains of rats. "It was an unproved assumption that VGF-derived peptides could regulate metabolism," the Italian team noted.

Exploring further, the researchers isolated TLQP-21 and injected it into the brains of lab mice every day for 14 days. At the same time, the mice were given high-fat diets that would normally trigger weight gain.

In this case, however, that didn't happen.

According to the researchers, the mice stayed slim because the peptide boosted their metabolic rate.

"When TLQP-21 is chronically injected into the cerebral ventricles, it increases [the mice's] energy expenditure and rectal temperature," Bartolomucci explained. Both of these changes signified a sped-up metabolism.

The peptide also affected key factors in metabolism and calorie-burning, he said. These included a rise in blood levels of the hormone epinephrine, as well as changes in locomotor and thyroid function.

Furthermore, in treated mice placed on a standard diet, "adipose [fat] tissue slightly decreased," Bartolomucci said. At the same time, the number of cellular receptors linked to fat-burning and energy expenditure rose.

All of this could explain why mice fed the high-fat diet kept their skinny physiques when they were given TLQP-21, Bartolomucci said.

The Italian researcher believes TLQP-21 has potential as an anti-obesity agent for use in humans. But he stressed that, "we are in an early stage of research. Indeed, this is the first study where the peptide is identified and the first study where its role in metabolic function has been tested."

Nonas agreed that it is a very big leap to assume that safety and efficacy in mice will translate to humans. First of all is the problem of drug-delivery.

"You can only do brain injections to a rat and a mouse," she pointed out. "You'd have to go a long way before you could take that and turn it into something that would work in a pill form or be injected into fat tissue."

The potential side effects of revving up the metabolism are also daunting. "You can have cardiac side effects, things like irregular heartbeat," Nonas said. "Then, there are headaches, heat and temperature-control things."

And even if people could eat high-fat diets without gaining weight, that doesn't mean they'd stay healthy. "We know plenty of people who are lean all their lives and still have clogged arteries from eating unhealthy foods," Nonas pointed out.

Any anti-obesity pill would only offer people a boost in fighting weight gain -- it would probably never be the total solution, she said.

In the meantime, people do have a proven, effective way of fighting or reducing obesity -- sensible diets and regular exercise.

"I'm not saying that that isn't really hard to do," Nonas said. "It will never be easy. But there will never be any magic bullet."

More information

There's more on healthy dieting at the American Dietetic Association.

SOURCES: Alessandro Bartolomucci, Ph.D., Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Rome; Cathy Nonas, director, obesity and diabetes programs, North General Hospital, New York City, and spokeswoman, American Dietetic Association; Sept. 18-22, 2006, Proceedings of the National Academy of Sciences
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