Activation of the central nervous system in obese Zucker rats during food deprivation

This study was carried out to investigate the pattern of neuronal activatio ns that occur in the obese fa/fa Zucker rat during food deprivation. The fu nctional activation of neurons was estimated in lean and obese Zucker rats either fed ad libitum or food-deprived for 3, 6, 12, and 24 hours by assess ing the expression of the immediate early gene c-fos. To identify the neuro ns instigating the activation of the hypothalamic-pituitary-adrenal axis in food-deprived obese rats, the retrograde tracer cholera toxin B subunit wa s injected in the parvocellular division of the paraventricular hypothalami c nucleus of obese rats and colocalized with e-fos mRNA during food depriva tion. The expression of e-fos was barely detectable in food-deprived lean r ats as well as in lean and obese animals fed ad libitum. However, 3 hours o f food deprivation were sufficient to significantly induce c-fos in the par aventricular thalamic nucleus of obese rats. In addition, 6 and 12 hours of food deprivation resulted in the activation of regions that are similarly stimulated in "neurogenic" stresses. These regions include the parvocellula r division of the paraventricular hypothalamic nucleus, the lateral septum, the basolateral amygdala, and some areas of the cortex. The highest number of neurons projecting to the parvocellular division of the paraventricular hypothalamic nucleus and revealing c-fos mRNA was, however, located in the paraventricular thalamic nucleus. In summary, the present results demonstr ate in the obese fa/fa Zucker rats, that food deprivation leads to brain ac tivations, which are in large part, similar to those induced by a "neurogen ic" stress and that the paraventricular thalamic nucleus is involved in thi s response. These changes could contribute to the development of hyperphagi a and obesity. J. Comp. Neurol. 441:71-89, 2001. (C) 2001 Wiley-Liss, Inc.