The role of neuropeptide Y in the antiobesity action of the obese gene product.
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.
Stephens
T W
TW
Technology Core Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Basinski
M
M
Bristow
P K
PK
Bue-Valleskey
J M
JM
Burgett
S G
SG
Craft
L
L
Hale
J
J
Hoffmann
J
J
Hsiung
H M
HM
Kriauciunas
A
A
D000818:Animals; D001835:Body Weight; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004435:Eating; D004926:Escherichia coli; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D066298:In Vitro Techniques; D020738:Leptin; D051379:Mice; D009478:Neuropeptide Y / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D020738:Leptin; D009478:Neuropeptide Y; D011506:Proteins; D011994:Recombinant Proteins