Decreased hypothalamic concentration of neuropeptide Y correlates with onset of hyperphagia in fa/ fa rats on postnatal day 12

Abstract

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.