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Endocrinology, Vol 132, 1939-1944, Copyright © 1993 by Endocrine Society

ARTICLES

Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse

JP Wilding, SG Gilbey, CJ Bailey, RA Batt, G Williams, MA Ghatei and SR Bloom
Division of Endocrinology and Metabolism, Royal Postgraduate Medical School, London, United Kingdom.

The obese hyperglycaemic ob/ob mouse exhibits hyperphagia and other abnormalities of hypothalamic function. We measured hypothalamic concentrations of four peptides implicated in the control of appetite and energy expenditure, neuropeptide-Y (NPY), neurotensin, galanin, and somatostatin, by RIA and their respective mRNAs using semiquantitative Northern blotting. Using lean (+/+) mice as controls, we found unchanged concentrations 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). Centrally administered neurotensin decreases food intake, whereas NPY potently stimulates food intake. An increase in NPY gene expression together with reductions in neurotensin concentration and mRNA in the hypothalamus may be implicated in the development of hyperphagia and other neuroendocrine abnormalities seen in the ob/ob mouse.


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