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Elevated Neuropeptide Y in the Arcuate Nucleus of Young Obese Zucker Rats May Contribute to the Development of Their Overeating¹

INSERM U.308 Mécanismes de Régulation du Comportement Alimentaire, 54000 Nancy ^* INSERM U.177, Paris, France

Neuropeptide Y (NPY) mediates feeding behavior through a local hypothalamic network formed by the arcuate and paraventricular nuclei (the AP axis). In the hypothalamus, NPY is mainly synthesized in neurons of the arcuate nucleus. These neurons project to the paraventricular nucleus, the site where NPY has the strongest stimulatory effects on food intake of Sprague-Dawley rats. In the adult Zucker fatty rat (a genetic model of obesity with a well-established hyperphagia), NPY concentrations in these nuclei are higher than in its lean counterpart. We measured hypothalamic NPY before the appearance of altered eating behavior, e.g., in very young (16-d-old) lean and obese Zucker pups, and in pups at an age when overeating had begun, e.g., a few days after weaning at 30 d. At 30 d, NPY concentrations were significantly higher in obese than in lean rats in the arcuate nucleus (14.2 ± 0.7 vs. 11.6 ± 0.5 pmol/mg protein, P < 0.01.). This difference was not observed at 16 d. A 160% increase was noted in the paraventricular nuclei of obese rats between 16 and 30 d of life compared with a 100% increase in the lean rats (P < 0.001). Neuropeptide Y concentration was greater in 30-d-old rats than in 16-d-old rats in other areas involved in the regulation of feeding behavior, such as the dorsomedian nuclei and lateral hypothalamus, but the values did not differ between genotypes. Higher NPY concentration was therefore detected early in young obese rats in the main hypothalamic site of NPY synthesis. Because the change in NPY concentration in the paraventricular nucleus was greater in obese rats than in lean rats between 16 and 30 d, the AP axis seemed overactivated in young obese rats. These changes coincided with changes in eating behavior. Because a comparable phenomenon has already been described in another NPY network including the suprachiasmatic nuclei, the internal clock regulating feeding rhythms, we conclude that NPY plays a major role in the development of overeating in the Zucker fatty rat.

KEY WORDS: • neuropeptide Y • hyperphagia • obesity • hypothalamic network • Zucker rats

¹ Presented at the 21st Annual Meeting of the Society for Neurosciences, November 1991, New Orleans, LA [Beck, B., Burlet, A., Bazin, R., Nicolas, J-P. & Burlet, C. (1991) Coexistence of increase in neuropeptide Y (NPY) with the beginning of hyperphagia in the obese Zucker rat. Soc. Neurosci. Abstr. 17: 193 (abs. 81.11)].

² To whom correspondence and reprint requests should be addressed at the current address: INSERM U.308, 38 rue Lionnois, 54000, Nancy, France.

Manuscript received 9 July 1992. Revision accepted 7 January 1993.

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