( c experiments designed to tease out exa...)An essential regulator of body weight revealed

"So I think it's fair to say the POMC neurons gained in stature during the last 10 years as being really important to feeding; meanwhile, the importance of the NPY pathway diminished. To some extent, the field began to think these cells were supporting players, but not really important," said Palmiter.

Now, however, Palmiter's lab has taken a different approach, and demonstrated definitively that NPY/AgRP neurons are essential for regulating eating behavior and the regulation of body weight. "We've put these neurons back on the map as being very, very important for feeding," he said.

Scientists first became interested in NPY/AgRP neurons in the early 1980s, when they found that one of the proteins they produce, NPY, triggers voracious eating behavior when injected into the brains of rats. High levels of NPY in the brain of both hungry and obese mice provided further evidence that NPY was likely to stimulate feeding.

Ten years ago, Palmiter's lab created mice that lacked the NPY protein, expecting that they would eat less than normal mice. "We thought they might chronically eat less than normal mice, and hence be lean ?maybe even starve," Palmiter said. But in fact, the feeding behavior of mice without NPY seemed no different than that of their normal counterparts. Something else, they decided, must be mediating NPY/AgRP neurons' ability to stimulate appetite.

"We were delighted," Palmiter said, "when, a few years later, agouti-related protein was discovered." That protein, which is found only in NPY/AgRP neurons, blocked appetite-suppressing signals from POMC neurons ?suggesting it could stimulate appetite through a mechanism unique from that of NPY. It seemed to be the molecule they'd been sear
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Source:Howard Hughes Medical Institute