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

TW Stephens, M Basinski, PK Bristow… - Nature, 1995 - nature.com
TW Stephens, M Basinski, PK Bristow, JM Bue-Valleskey, SG Burgett, L Craft, J Hale…
Nature, 1995nature.com
RECENTLY Zhang et al. 1 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 homolo-gues for this
gene are known1, 2. Previous experiments3, 4 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 …
Abstract
RECENTLY Zhang et al.1 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 homolo-gues for this gene are known1,2. Previous experiments3,4 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 target5. 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 hypo-thalamus. One mechanism by which this protein regulated food intake and metabolism was inhibition of neuropeptide-Y synthesis and release.
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