Scientists have identified the brain cells that regulate appetite. Problems with the way they work could be behind disorders such as excessive eating or obesity.
Working on mice, whose appetites are controlled in a similar way to humans, researchers found that a certain group of cells were essential for the animals to eat properly: without them, the adult mice stopped eating. Serge Luquet at the University of Washington and Richard Palmiter of the Howard Hughes Medical Institute in Maryland, who led the work, publish their results today in Science.
The brain works out when and what to eat thanks to a small group of cells called the arcuate nucleus. This area of the brain receives a myriad hunger signals via hormones such as insulin, leptin and ghrelin. These help the brain work out whether the body has enough calories and nutrients. If the brain calculates there are not enough calories in the body, it responds with a hunger signal.
The brain cells come in two flavours. The first to be discovered was the POMC, which sends signals to reduce appetite. Mice with defects in these neurons rapidly become obese.
The second type of neuron is named after the two proteins it produces, neuropeptide Y and agouti-related protein. This NPY/AgRP neuron has long been suspected as acting in opposition to the POMC, there to stimulate appetite. But experiments so far had failed to prove any conclusive link between the chemicals produced by the neuron and feeding behaviour. In the new study, Prof Palmiter decided to look at the neurons themselves, removing them from mice.
Unlike humans, mice are not susceptible to the toxin produced by diphtheria bacteria. The researchers genetically engineered the NPY/AgRP neurons in the mice and infected them with diphtheria, thereby killing the cells. Prof Palmiter then monitored how much the mice ate. The effects were dramatic: after being infected with the diphtheria toxin, the animals ate less and by the eighth day, many had lost a fifth of their body weight.
The researchers also found that removing the neurons of mice less than eight days old made no difference to their feeding habits. "Killing these neurons before they're functionally engaged gives the developing mouse brain a way to compensate," said Prof Palmiter. "But it's still a tall challenge. You're asking some other neuron, presumably, to either increase what it normally does, or to do something that it never did before."
Neuroscientists believe that the NPY/AgRP and POMC neurons do the same thing in humans. "I would predict that if you could do the experiment in humans, this result would be the same, because the circuits are the same," said Prof Palmiter. He speculated that mutations in the human genes which affect the survival of these neurons or their ability to respond to hormones might alter when a person eats or regulates their body weight.
