Response of neuropeptide Y-deficient mice to feeding effectors.
Neuropeptide Y (NPY) is thought to be an important central regulator of feeding behavior and body weight. However, mice lacking NPY due to targeted genetic deletion do not display abnormalities in food intake or body weight with ad libitum access to food or in response to fasting. In this study, we investigate the response of NPY-deficient (NPY-/-) mice to anorexic and orexigenic treatments. The dose-dependent stimulation of food intake by central NPY administration was unaltered in NPY-/- mice. Peripheral administration of various doses of leptin for 2 days elicited a two-fold greater inhibition of food intake in NPY-/- mice than in wildtype (NPY+/+) mice. In addition, lateral ventricular administration of leptin (1 microg) suppressed refeeding in NPY-/- mice after a 24 h fast, but had little effect in NPY+/+ mice. However, the response to other feeding inhibitors such as corticotrophin releasing factor (CRF), dexfenfluramine, and a melanocortin 4 receptor (MC4R) agonist, MTII, was unaltered in NPY-/- mice. These results indicate that the appetite-suppressant action of exogenous leptin is uniquely amplified in NPY-/- mice, and suggest that NPY may tonically antagonize leptin action.
Hollopeter
G
G
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle 98195, USA.
Erickson
J C
JC
Seeley
R J
RJ
Marsh
D J
DJ
Palmiter
R D
RD
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D020372:Dexfenfluramine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D007276:Injections, Intraventricular; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments; D019894:Peptide YY / Q000494:pharmacology; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000819:agonists; D015398:Signal Transduction; D000521:alpha-MSH / Q000031:analogs & derivatives
D020738:Leptin; D009478:Neuropeptide Y; D009842:Oligopeptides; D010446:Peptide Fragments; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D019894:Peptide YY; C061785:peptide YY (3-36); D000521:alpha-MSH; D003346:Corticotropin-Releasing Hormone; D020372:Dexfenfluramine