This book presents a broad summary of current knowledge concerning the structure and biochemistry of neuropeptide Y in relation to its role in feeding and interactions with receptors, transducers, effectors and channels that can also connect to food intake. The very high conservation of NPY sequence indicates its critical importance in basal metabolic regulation. Mutations connecting to NPY are virtually absent, and those affecting the Y1 and Y2 receptors are very few. From the evidence presented across vertebrate classes, NPY appears mainly as metabotropic driver via the Y1 group of receptors, and its negative metabotropicity through the Y2 receptor is only of importance in the mammal, and then tempered by Y2 receptor masking in the hypothalamus and low numbers in the cortex, and by low availability of NPY outside the forebrain. Anatomically, NPY is well-represented especially in limbic areas of the forebrain, but the feeding-critical presence of Y1 receptors is, at least in the rodent, highest in the neocortex, and evidence presented in this book points to much larger involvement of cortical NPY receptors in feeding regulation than is usually perceived. The strong presence of this highly conserved peptide in the vertebrate forebrain is increasingly documented as linked not only to the regulation of glucose metabolism (and insulin activity), but also as directly involved in the operation of transducers, effectors and channels. This should be enabled especially by the high interactivity of the acidic sector of NPY (which is not shared by NPY-related systemic peptides, peptide YY and pancreatic polypeptide), and results in partial agonism and possibly also in accumulation in the bilayer. NPY could be involved as a helper agonist in several parts of the vertebrate metabolome.
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