BioEd Online

There is a building block of protein that kills hunger in the brain, researchers have shown in experiments with rats. The result backs the idea that altering tiny quantities of particular nutrients in our diets could help fight obesity and disease.

The study suggests that rats' brains monitor levels of amino acids, the components of proteins, and use this to judge how much food to eat. The researchers, at the University of Cincinnati, Ohio, found that injecting an amino acid called leucine into the brains of hungry rats curbed their appetite: they gained a third less weight over 24 hours than rats that didn't have jabs. The team reports its results in Science¹.

The discovery implies that traditional thinking about diets — based on monitoring the broader classes of carbohydrates, fats and proteins — is rather crude.

Tinkering with our diets more subtly, to include particular cocktails of 'micronutrients' such as amino acids, sugars or fat components, might help to control weight, alter aspects of metabolism and perhaps combat disease.

Nutrient cocktails

"We have to stop thinking of nutrients as just energy or protein sources," says Luciano Rossetti at Albert Einstein College of Medicine in New York City, who is a proponent of this more subtle approach to diet. Micronutrients are also biologically active molecules, he points out.

Earlier studies have shown that lowering levels of oleic acid, the major fatty component of olive oil, could dampen animals' appetites, says Rossetti. And eating the amino acid L-phenylalanine, which is found in some vegetables, juices, yogurt and artificial sweeteners, has been shown to release a hormone called cholecystokinin, which in turn seems to suppress human appetite².

The notion that leucine gleaned from protein in foods, such as meat and eggs, might do the same by having a direct impact on the brain is so far speculative. The team doesn't know for sure whether leucine needs to be injected to penetrate the brain, nor do they know if it works in humans to suppress appetite.

"My worst fear is that someone is going to be selling leucine on the Internet because of this," says Randy Seeley, who led the research.

Brain food

Certain neurons in the brain's hypothalamus carefully regulate our appetite and weight, by monitoring long-term fat stores. In the past few years, researchers have also started to understand how the same circuits keep an eye on the minute-by-minute changes in circulating nutrients.

Seeley's team studied a protein called mTOR (mammalian target of rapamycin), which is known to work in most cells of our bodies to detect fuel levels and decide whether an individual cell has the resources to grow. The researchers wanted to see whether it also senses fuel in the brain, and so directs an animal's eating behaviour as a whole.

The team found that mTOR is active in the neurons that control appetite in the hypothalamus, and that leucine boosts the activity of mTOR. This makes rats eat less than they would normally. The researchers also showed that leptin, a hormone that tells the body how much fat we are carrying, activates mTOR as well.

The team proposes that mTOR may be a molecule central to appetite control, although probably one of many. The various weight-control hormones such as leptin, plus the circulating fats, sugars and proteins could all influence the activity of mTOR, which in turn would regulate feeding.

"This idea could integrate all those things very nicely," says Martin Myers, who studies mechanisms of appetite control at University of Michigan Medical School in Ann Arbor.

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