INCREASED NEUROPEPTIDE-Y MESSENGER-RIBONUCLEIC-ACID (MESSENGER-RNA) AND DECREASED NEUROTENSIN MESSENGER-RNA IN THE HYPOTHALAMUS OF THE OBESE (OB OB) MOUSE/

The obese hyperglycaemic ob/ob mouse exhibits hyperphagia and other ab normalities of hypothalamic function. We measured hypothalamic concent rations of four peptides implicated in the control of appetite and ene rgy expenditure, neuropeptide-Y (NPY), neurotensin, galanin, and somat ostatin, by RIA and their respective mRNAs using semiquantitative Nort hern blotting. Using lean (+/+) mice as controls, we found unchanged c oncentrations of NPY, galanin, and somatostatin and a 25% reduction in neurotensin (P < 0.01). Neurotensin mRNA was similarly decreased (by 30%; P < 0.02), while NPY mRNA was increased 3-fold (P < 0.01). Centra lly administered neurotensin decreases food intake, whereas NPY potent ly stimulates food intake. An increase in NPY gene expression together with reductions in neurotensin concentration and mRNA in the hypothal amus may be implicated in the development of hyperphagia and other neu roendocrine abnormalities seen in the ob/ob mouse.