Can't Control Your Appetite? Here's Why

Researchers discover why it's so difficult to knock off those extra pounds.

ByLee Dye
October 07, 2008, 7:27 PM

Oct. 8, 2008— -- Want another reason why you shouldn't spend too much time at the trough? Because consistently eating too much food over a period of just a few weeks can screw up your brain, taking away your ability to control your appetite.

That's the basic finding in a new study out of the University of Wisconsin-Madison that could help explain why once you've put on those extra pounds, it's really hard to take them off. The study is published in the current issue of the journal Cell.

"We've discovered why the appetite doesn't shut down," said Dongsheng Cai, assistant professor of physiology at UW-Madison, in a telephone interview, even after a person has consumed enough food to maintain the correct balance between calorie intake and energy expended.

The answer lies in a normally inactive "pathway" through a critical part of the brain that springs to life after at least a couple of months of "overnutrition," he said. A pathway is a course by which brain cells transmit impulses from their origin to their destination. But in this case, a normally dormant pathway is re-energized and interferes with "signaling" that should tell the brain you've had enough to eat.

"We're not talking about one day, or even a few days" of overeating, Cai said. "It's not too long. Two or three months of overnutrition, a diet high in fat and sugar," can wake up the pathway, he said.

Once the pathway is mobilized, he said, it can "lead to a number of dysfunctions, including resistance to insulin and leptin." Leptin is a fat hormone essential for appetite control. Insulin lowers blood sugar by causing cells to extract it from the bloodstream. Both are critical to maintaining the balance between caloric intake and energy expenditures.

The good news is it may be possible to shut down that apparently obsolete pathway in the brain, thus restoring an obese person's ability to control his or her appetite. It's significant that the activation of the pathway preceded obesity in lab mice, so it is clearly part of the cause of weight gain, not just the result.

"These experiments and results indicate that oversupply of general nutrients can acutely activate the hypothalamic [pathway] before the onset of obesity," the study says.

Cai and his colleagues have focused their research on the hypothalamus, the part of the brain that for the past 10 to 15 years has been recognized as the brain's "headquarters" for maintaining an energy balance. They used lab mice for their research, since it's not practical to dissect human brains after an extended period of overeating, but they are confident the findings will apply to humans as well.

"Many pathways established in animals are exactly the same in humans," Cai said.

The same type of pathway actually plays a critical role throughout the entire body's immune system, but it has no known function in the hypothalamus. Cai speculates that it may be a remnant from an ancient immune system that is no longer active.

In their paper, the researchers identify the pathway as "a master switch and central regulator" of the body's immune system, so just simply turning it off would be disastrous. The challenge is to come up with a way, possibly medication or genetic engineering, to keep the pathway alive for the immune system, but keep it dormant in the hypothalamus, where apparently all it does is cause trouble. That could take years, of course, even assuming the basic findings are born out by further research.

The research indicates that the critical signaling function of two hormones, insulin and leptin, is disrupted when the pathway in the hypothalamus is activated.

"Insulin is a hormone secreted by the pancreas, and leptin is another type of hormone secreted by fat tissue," Cai said. "When we have obtained enough calories, these two hormones travel to the brain and tell the hypothalamus it's time to stop eating, you have enough calories.

"But these two message systems can be interrupted by the activation of the pathway we've discovered, so the appetite doesn't shut down," he said.

It's also likely that the message telling the brain to increase energy expenditure is also shut down, Cai said. So, instead of going out and walking off those excess calories, the dieter takes a nap.

That plunges the person into a downward spiral, eating more and more, and putting on more and more pounds. The sentinels that are supposed to maintain the correct balance between caloric consumption and energy expenditure remain silent, deactivated by the reactivation of a part of the brain that shouldn't be there.

"Our work marks an initial attempt to study whether inhibiting an innate immune pathway in the hypothalamus could help to calibrate the set point of nutritional balance and therefore aid in counteracting energy imbalance and diseases induced by over-nutrition," the report states.

In other words, maybe there's a way here to reset the appetite and make it a lot easier to knock off those extra pounds. The research also suggests that in some cases, there's more at work than simply a lack of willpower when it comes to losing weight.

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