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Neuropeptide Y (NPY) is the most abundant neuropeptide in the brain. It is a member of a family of proteins that include pancreatic polypeptide, peptide YY and seminalplasmin. In addition to its function in feeding behavior, several other physiologic roles have been assigned to NPY, including involvement in circadian rhythms, sexual function, anxiety responses and vascular resistance.
NPY is known to be an extremely potent stimulator of feeding behavior. Feeding behavior in rodents is blocked by injection of antibodies or antisense RNAs against NPY. More importantly, leptin appears to act, at least in part, by inhibiting NPY synthesis and release in the hypothalamus. Additionally, mutations that interfere with signalling via the hypothalamic melanocortin-4 receptor lead to obesity that is at least partially explained by perturbations of NPY expression.
Although NPY is clearly involved in control of food intake, the complexity and apparent redundancy of that system is illustrated by recent experiments in which the NPY gene was disrupted in mice. Surprisingly, mice homozygous for targeted disruption of the NPY gene maintained normal body weight and retained normal responses to leptin. Indeed, they were normal in all respects except for increased susceptibility to seizures. When the NPY knockout mice were mated with ob/ob mice (homozygous disruptions of the gene encoding leptin), the resulting "double mutants" became less obese than ob/ob mice. The tenative conclusion from these experiments is that leptin's effect on body weight is mediated in part by its effect on NYP expression, but that other systems have overlapping control over food intake and energy expenditure.
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