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

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


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.

MeSH terms

  • Animals
  • Body Weight
  • Cell Membrane / metabolism
  • Diabetes Mellitus, Experimental / metabolism
  • Eating
  • Escherichia coli
  • Humans
  • Hypothalamus / physiology
  • In Vitro Techniques
  • Leptin
  • Mice
  • Neuropeptide Y / physiology*
  • Obesity / genetics*
  • Proteins / genetics
  • Proteins / physiology*
  • Rats
  • Recombinant Proteins / pharmacology


  • Leptin
  • Neuropeptide Y
  • Proteins
  • Recombinant Proteins