Curing Resistance to Fat Hormone Sheds Pounds

Jan. 16, 2004 -- Overcoming an obese person's natural resistance to a fat-fighting hormone may be the first step in reaching a healthy weight.

A new study shows that rats that were cured of this resistance through gene therapy ate less and exercised more, even though they were offered the same high-fat diet that made them overweight in the first place.

"It was a voluntary reduction in energy intake," says researcher Satya Kalra, professor of neuroscience at the University of Florida. "The refrigerator was open, but they decided to eat less. That's the interesting part of it."

Unlocking Leptin

Leptin is a hormone produced in animal fat cells that helps regulate body weight by stimulating the brain to give a feeling of fullness and reduce appetite. But researchers say the problem is that overweight animals have too much fat, which leads to excessive leptin production and dampens this fat-fighting effect.

In this study, published in the December 2003 issue of Obesity Research, researchers looked at whether gene therapy could help obese rats overcome this leptin resistance. Thirty adult rats were divided into two groups: one group was fed a standard diet containing 11% fat and the others went on a high-calorie diet and ate a feed containing 45% fat.

After 80 days, the average weight of the rats on the high-fat diet increased by 20%. At that point, six of the obese rats were given an injection of a gene that produces leptin directly in their brains and six were given a placebo.

Fifty-six days after the injections were given, the weight of the obese rats given the leptin gene had dropped to only 3% above their beginning weight. Those given the placebo remained 20% heavier than their beginning weight.

Kalra says the rats were still offered as much of the high-fat food as they wanted. But after getting the gene therapy, they opted to eat 10%-15% less and increased their energy expenditure on their own.

Blood levels of leptin in the obese rats that got the leptin gene naturally dropped as they lost excess fat, but Kalra says they also produced more leptin in the brain, where the hormone has the biggest impact on influencing behavior.

Kalra says applying this technique to humans would require neurosurgery as well as gene therapy, which means any human studies are several years down the road. But by applying what they learned in these rat studies, they may eventually be able to develop other ways to help humans overcome leptin resistance without surgery.