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. 1995 Oct 12;377(6549):530-2.
doi: 10.1038/377530a0.

The role of neuropeptide Y in the antiobesity action of the obese gene product

T W Stephens  1 , M Basinski, P K Bristow, J M Bue-Valleskey, S G Burgett, L Craft, J Hale, J Hoffmann, H M Hsiung, A Kriauciunas, et al.
Affiliations

The role of neuropeptide Y in the antiobesity action of the obese gene product

T W Stephens et al. Nature. .

Abstract

Recently Zhang et al. cloned a gene that is expressed only in adipose tissue of the mouse. The obese phenotype of the ob/ob mouse is linked to a mutation in the obese gene that results in expression of a truncated inactive protein. Human and rat homologues for this gene are known. Previous experiments predict such a hormone to have a hypothalamic target. Hypothalamic neuropeptide Y stimulates food intake, decreases thermogenesis, and increases plasma insulin and corticosterone levels making it a potential target. Here we express the obese protein in Escherichia coli and find that it suppresses food intake and decreases body weight dramatically when administered to normal and ob/ob mice but not db/db (diabetic) mice, which are thought to lack the appropriate receptor. High-affinity binding was detected in the rat hypothalamus. One mechanism by which this protein regulated food intake and metabolism was inhibition of neuropeptide-Y synthesis and release.

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