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WEDNESDAY, March 17 (HealthDayNews) -- Scientists have found another link in the complex chain of biological events that govern how much we eat and, consequently, what we weigh.

This time, the link is an enzyme called AMP-activated protein kinase (AMPK), which is found, among other areas, in the hypothalamus region of the brain. The enzyme appeared to have an effect on regulating how much mice ate and how heavy they grew, a new study finds.

The finding could potentially make the enzyme a target for a drug to fight obesity, which is rapidly becoming the preeminent American health crisis of the 21st century.

"The exciting thing is to find some physiologic and biochemical explanation for appetite and for hunger," says Dr. Christine Ren, director of the Surgical Weight Loss Program at New York University Medical Center in New York City. "If we can define the pathway [involved in] hunger and appetite and satiety, then we can find a solution or some sort of medication to block it."

Dr. Nicholas Mezitis is director of the Mezitis Research and Education Institute for Obesity, and an attending physician of endocrinology, diabetes and nutrition at St. Luke's-Roosevelt Hospital Center in New York City. He says "research is ongoing to assess the signals that relate to satiety and any mechanisms that might influence satiety, because there's great interest in generating some kind of product to give to people to regulate eating behavior."

The authors of the new study, which appears in the March 18 issue of Nature, have long focused on the various signaling pathways within the body that can contribute to both obesity and its corollary, type 2 diabetes.

"Any step in that pathway is potentially a drug target for obesity or type 2 diabetes," says study author Dr. Barbara Kahn, chief of the division of endocrinology, diabetes and metabolism at Beth Israel Deaconess Medical Center in Boston.

For this study, Kahn and her colleagues focused even more closely on a pathway regulated by the AMPK enzyme, which has been variously described as a "fuel gauge," "cellular energy sensor" or "stress-activated pathway."

The stress referred to here isn't psychological but related to more basic survival needs, like having enough food. The AMPK enzyme is activated when there's not enough energy in the cells. "The cell would be getting a signal that it needs energy and that would translate into increased appetite," Mezitis says.

Kahn had already discovered AMPK has a relationship with leptin, an important hormone that is produced by fat cells and regulates food intake and energy expenditure, such as levels of physical activity. In skeletal muscle, leptin activates AMPK, which leads to increased utilization of fatty acids.

While leptin is at work in different parts of the body, one area is critical. "The salient action is in the brain, specifically in this area called the hypothalamus," Kahn says.

For the study, Kahn wanted to see if, in addition to the skeletal muscle, leptin also regulated AMPK in the hypothalamus.

"It turns out, yes, it does, but the regulation is opposite. Leptin inhibits AMPK in the hypothalamus," Kahn explains. This makes sense because the net effect of leptin is to make a person eat less and spend more energy, so inhibiting AMPK also leads to a suppression of food intake, Kahn says.

But it's not just leptin that regulates the activity of AMPK in the hypothalamus. Fasting and eating also have an effect, which indicates that AMPK might be part of the signaling mechanism for hunger and satiety messages.

"One thing we know is that the vast majority of obese people develop resistance to leptin," Kahn says. "We don't yet know if [the AMPK] pathway also becomes resistant in obesity but we're looking at that. It would be plausible." If this were true, it might play an important role in leptin resistance in the vast majority of obese people, she says.

When the researchers injected the form of AMPK that was always active into the hypothalamus, leptin didn't work. "If this enzyme is always activated, the animal is resistant to leptin," Kahn says. Leptin tells us when to eat and when not to eat, so its disruption would have consequences in terms of obesity.

"Humans and rodents with specific genetic defects so they do not make leptin or who have mutations in the leptin receptor causing impaired action of leptin are extremely obese," Kahn adds.

"AMPK blocks leptin from giving the signal to stop eating and, if leptin is going to be successful, then you'll have to block AMPK," Mezitis says.

While this may not be the answer to the cause of obesity, it's certainly part of an overall answer, Ren says.

"Hunger is very primitive and starts in the hypothalamus, which is where they found this chemical," Ren says. "It's so primitive that the body will protect that feeling 20 different ways. If one chemical doesn't preserve the feeling of hunger, another chemical will. It's exciting that we found one chemical. However, there are 19 more."

More information

For more on obesity, visit the U.S. Centers for Disease Control and Prevention. The American Diabetes Association has more on type 2 diabetes.

(SOURCES: Barbara B. Kahn, M.D., chief, division of endocrinology, diabetes and metabolism, Beth Israel Deaconess Medical Center, and professor, medicine, Harvard Medical School, both in Boston; Nicholas Mezitis, M.D., assistant professor, clinical medicine, Columbia University, director, Mezitis Research and Education Institute for Obesity, and attending physician, division of endocrinology, diabetes and nutrition, St. Luke's-Roosevelt Hospital Center, New York City; Christine Ren, M.D., director, Surgical Weight Loss Program, New York University Medical Center, and assistant professor, surgery, New York University School of Medicine, New York City; March 18, 2004, Nature)

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