EARLY MODIFICATION OF NEUROPEPTIDE-Y BUT NOT OF NEUROTENSIN IN THE SUPRACHIASMATIC NUCLEUS OF THE OBESE ZUCKER RAT

Hyperphagia in the obese Zucker rat is characterized by the early modification of the dark/light (D/L) rhythm of food intake. This rhythm is mainly driven by the suprachiasmatic nucleus (SCN) and, more controversially, by the ventromedian nucleus (VMN). In the SCN of adult obese Zucker rat, the concentrations of neuropeptide Y (NPY), a potent stimulator of food intake, are increased whereas those of neurotensin (NT), an anorexigenic peptide, are decreased. However, nothing is actually known about the synchronicity of the dysregulation of the D/L rhythm and variations of these peptides. That is why we measured NPY and NT in the microdissected SCN and VMN of lean (n = 16) and obese (n = 15) Zucker rats before the occurrence of hyperphagia (day 16 of age) and a few days after weaning (day 30 of age) when the modifications are apparent. For NPY, there was a very significant effect of age (P < 0.001) for both nuclei and a significant effect of genotype (P < 0.02) for the SCN only. NPY concentrations increased between 16 and 30 days in both nuclei (+74% (SCN) and +70% (VMN) in the obese rat; +57% (SCN) and +67% (VMN) in the lean rat; P < 0.001). NPY in the SCN was not different at 16 days of age between lean and obese rats but significantly increased at 30 days in the obese rat (22.6 +/- 1.2 vs. 18.6 +/- 1.5 ng/mg protein; P < 0.05). NT was not detected in the SCN of either group at 16 days or at 30 days. In the VMN, NT concentrations were very similar in both groups whatever the age considered and amounted to about 1 ng/mg protein. This study supports, therefore, the major role of the SCN in the regulation of feeding patterns. Neurotensin likely plays an additional later role in this process whereas the early rise of NPY in the SCN suggests that this orexigenic peptide could play an important role in the establishment of the abnormal D/L rhythm of food intake found in the adult obese Zucker rats.