Decreased hypothalamic concentration of neuropeptide Y correlates with onset of hyperphagia in fa/fa rats on postnatal day 12.
An increased action of hypothalamic neuropeptide Y (NPY) has been proposed as a major factor in the pathophysiology of the obesity syndrome in Zucker (fa/fa) rats. Using a developmental strategy to test this hypothesis, we showed previously that significantly more arcuate NPY was expressed in fa/fa pups than in lean littermates on postnatal day (P) 2 and throughout the preweaning period [Physiol. Behav. 67 (1999) 521], and that hyperphagia first appeared on P12 [Am. J. Physiol. 275 (1998) R1106]. To test the hypothesis further, we used a specific radioimmunoassay to measure the concentration of hypothalamic NPY peptide in lean (+/+ and +/fa) and obese fa/fa Zucker rat pups on P9, P10, and P12. The concentration of NPY in fa/fa pups was not significantly different from that of the other genotypes. There was, however, a significant decrease in NPY concentration from P9 to P12 in fa/fa pups, but not in lean pups. The combination of increased NPY message and decreasing concentration of NPY peptide in fa/fa pups with age is consistent with, but does not prove, increased release of hypothalamic NPY in fa/fa pups just before and on P12 when hyperphagia emerges. These results provide further support for the importance of hypothalamic NPY in the phenotypic expression of hyperphagia in the fa/fa pups during the second postnatal week.
Ster
Andrea M
AM
Department of Psychiatry, E.W. Bourne Laboratory, Weill Medical College of Cornell University and New York Presbyterian Hospital, White Plains, NY 10605, USA.
Kowalski
Timothy J
TJ
Dube
Michael G
MG
Kalra
Satya P
SP
Smith
Gerard P
GP
D000375:Aging / Q000502:physiology; D000818:Animals; D005260:Female; D005838:Genotype; D006963:Hyperphagia / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D010641:Phenotype; D051381:Rats; D011924:Rats, Zucker
D009478:Neuropeptide Y