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Am J Physiol Regul Integr Comp Physiol 284: R1560-R1566, 2003. First published February 6, 2003; doi:10.1152/ajpregu.00557.2001
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Vol. 284, Issue 6, R1560-R1566, June 2003

Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats

Amit Varma1, Jing He1, Lisa Weissfeld2, and Sherin U. Devaskar1

1 University of Pittsburgh Schools of Medicine; 2 Public Health, Pittsburgh, Pennsylvania 15213-3180; and 3 Department of Pediatrics, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California 90095-1752

We investigated the effect of repetitive postnatal (2-7 days) intracerebroventricular administration of neuropeptide Y (NPY) on food intake and body weight gain in the 3- to 120-day-old Sprague-Dawley rats. NPY caused a 32% transient increase in body weight gain with elevated circulating insulin concentrations within 24 h. This early intervention led to the persistence of hyperinsulinemia and relative hyperleptinemia with euglycemia in the 120-day-old female alone. This perturbation was associated with 50% suppression in adult female hypothalamic NPY concentrations and a 50-85% decline in NPY immunoreactivity in the paraventricular and arcuate nuclei. This change was paralleled by a ~20% decline in food intake and body weight gain at 60 and 120 days. However, when exogenous NPY was stereotaxically reinjected into the paraventricular nucleus of the ~120-day-old adult females who were pretreated with NPY postnatally, an increase in food intake and body weight gain was noted, attesting to no disruption in the NPY end-organ responsivity. We conclude that postnatal intracerebroventricular NPY has long-lasting effects that predetermine the resultant adult phenotype in a sex-specific manner.

development; hypothalamus; food intake; hyperinsulinemia


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