'Eat Right' Enzyme Directs Healthy Eating

April 13, 2005 — -- We shouldn't need our mothers to tell us to finish our vegetables -- research shows our bodies are wired to let us know.

Neuroscientists working separately at the University of California at Davis and at New York University School of Medicine have revealed an ancient "switch" in some mammals that signals the appetite to seek foods with perfect nutritional balance.

The mechanism has been found in rats, mice, slugs, even yeast and, the researchers say, there's every reason to believe it also exists in people.

"It's a very simple mechanism that's present in very simple organisms," said David Ron of the New York University School of Medicine. "When you see that in biology it usually means it's an important mechanism that's present in all species, including humans."

The trick is finding a way to emphasize that switch over less-healthy ones -- like the impulse to scarf down large quantities of fat and sugar -- so that people might listen to it more diligently. As researchers point out, the signal to eat good nutrition is only one of a wide array of signals at play when it comes to appetite.

"Food intake is complicated," said Ann Kelley, a neuroscientist at the University of Wisconsin at Madison. "There are so many molecules in the brain that turn it on and off that no one has a clear definitive idea of how it all works."

The 'Eat Right' Signal

The switch for eating good nutrition is not a single mechanism, but a cascade of events that starts with an enzyme known as GCN2 kinase. When eating a food that's deficient in one of the 20 critical amino acids (the building blocks that make up proteins), the body detects the deficiency in the bloodstream and puts the brakes on appetite. This prevents the animal from eating too much of one thing -- say corn, which lacks the amino acid tryptophan, and triggers more foraging for foods that can complete their nutritional needs.

"This tells us that we have an innate mechanism for recognizing what's good for us to eat," said Ron, who published his results in the current issue of the journal Cell Metabolism.

Dorothy Gietzen of the University of California at Davis has found similar results in rats, mice, even slugs. When Gietzen knocked out the gene that serves up the critical enzyme switch, the animals continued to eat foods that lacked nutrition. Animals who had not been tampered with waited for something more nutritious to come along.

"If the amino acid is not there, they won't eat the diet," said Gietzen, who published her most recent results in the journal Science. "Their brains recognized that their diet was not good for them."

The problem is there are other, stronger signals that don't always tell us to choose the apple over the candy bar.

"The story goes that in evolution when we didn't have much food around, the instinct to eat food rich in calories was a good signal to have because high-fat foods store well," said Kelley.

Battle of Signals

Kelley's research has shown that a high-fat diet appears to alter the brain biochemistry through the release of reward signals, in a similar reaction to drugs such as morphine. This is due to the release of opioids -- "pleasure chemicals" in the brain -- that reduce the feeling of being full.

More studies by Dr. Sarah Leibowitz, a neurobiologist at Rockefeller University in New York, have shown that exposure to fatty foods might reconfigure the hormonal system to want more fat. In her research, rats fed a high-fat diet become more resistant to leptin -- the hormone that stops eating. At the same time, levels of galanin -- a peptide in the brain that stimulates eating and slows down energy expenditure -- increased.

"Imbalanced diets, whether rich in sugar or fat, interfere with normal satiety processes, causing resistance to hormones such as insulin and leading to overeating," she said.

This might explain why an estimated 129.6 million Americans, or 64 percent, are overweight or obese. When we're faced with high-fat and high-sugar options, it becomes difficult to fight the urge to indulge. Still, there is reason to hope that the body's healthier instincts can win out when it comes to appetite.

Studies of babies have shown that, when presented with a variety of unprocessed foods, infants instinctively eat a little of each to achieve perfectly balanced meals. Ron thinks this means the babies are tapping into the very primitive enzyme switch that cues for complete nutrition.

That said, in today's society, where most Americans face an abundance of food choices and struggle with an abundance of urges, there may be no signal as important as culture -- and being told to finish your vegetables.