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D.iet & H.ealth : B.ody W.eight Last Updated: Nov 12th, 2006 - 20:38:00

Appetite-Fighting Molecule May Fight Obesity
Oct 3, 2006, 21:42

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Early study in mice shows it cut weight gain in half

By Rick Ansorge
HealthDay Reporter

TUESDAY, Oct. 3 (HealthDay News) -- Japanese researchers have discovered a naturally occurring molecule that suppresses appetite in mammals, raising hopes that it might one day treat obesity in humans.

Over a period of 10 days, rats that received a continuous infusion of the compound, called nesfatin-1, ate significantly less food than untreated rats. They also gained significantly less weight than untreated rats (an average of 12.6 grams vs. an average of 30.4 grams), apparently without any adverse effects.

The findings, published in the Oct. 1 online edition of Nature, "indicate that nesfatin-1 might be a useful target for the development of drug therapies to treat obese persons," the study authors concluded.

A team led by Dr. Masatomo Mori, of the department of medicine and molecular science at Gunma University Graduate School of Medicine, in Maebashi, say they discovered the molecule after analyzing 596 genes, nine of which are expressed in both the brains and fat tissues of mammals.

The researchers narrowed their search to NUCB2, a protein secreted by the hypothalamus, a brain region that helps regulate appetite. They suspect that a fragment of NUCB2 -- a molecule they dubbed "nesfatin-1" -- plays a key role in appetite control.

To test their theory, they injected nestfatin-1 into the hypothalamus regions of a special strain of obese rats. These rats carried a gene mutation that led them to resist the effects of leptin, a hormone thought to play a role in obesity. Obese people are also thought to be somewhat resistant to leptin's appetite-dampening effects.

The injections appeared to decrease appetite in the rats, the researchers report, "suggesting that nesfatin-1 may be effective in obese persons with leptin resistance," Mori said.

In fact, "the dose we used had the same potency as leptin in reducing appetite," he said. Compared to rats that didn't get the injections, rats receiving nesfatin-1 ate much less and cut their weight gain by more than half.

In another experiment, the researchers used a special antibody to block nesfatin-1 uptake. The result: the rats' appetites rebounded and they quickly put on weight.

There were no major side effects, Mori said, and, "so far, we have not observed any adverse behavioral changes in rats receiving nesfatin-1."

Because brain injections are not a feasible treatment for obese humans, Mori and his team have been testing other ways of administering nesfatin-1 to obese rats.

"We have preliminary data showing that peripheral [non-brain] injection of nesfatin-1 is also effective to reduce food intake in rats," Mori said. "So we are optimistic that subcutaneous injection of nesfatin-1 may become available to treat human subjects with obesity."

Overweight and obesity are a global epidemic, in developing as well as developed nations. Of the estimated 1 billion adults worldwide who are overweight, about 300 million are considered obese, according to the World Health Organization.

Obesity is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension and stroke, and some forms of cancer.

"We are really hopeful that nesfatin-1 and [similar molecules] will prove useful in treating obese persons in the near feature," Mori said.

More information

There's more on research into fighting obesity at the U.S. National Institutes of Health.

SOURCES: Masatomo Mori, M.D., Ph.D., department of medicine and molecular science, Gunma University Graduate School of Medicine, Maebashi, Japan; Oct. 1, 2006, Nature online

Last Updated: Oct. 3, 2006

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