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

This study was carried out to investigate the pattern of neuronal activations that occur in the obese fa/fa Zucker rat during food deprivation. The functional 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 assessing the expression of the immediate early gene c-fos. To identify the neurons instigating the activation of the hypothalamic-pituitary-adrenal axis in food-deprived obese rats, the retrograde tracer cholera toxin B subunit was injected in the parvocellular division of the paraventricular hypothalamic nucleus of obese rats and colocalized with c-fos mRNA during food deprivation. The expression of c-fos was barely detectable in food-deprived lean rats as well as in lean and obese animals fed ad libitum. However, 3 hours of food deprivation were sufficient to significantly induce c-fos in the paraventricular 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 parvocellular 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 demonstrate in the obese fa/fa Zucker rats, that food deprivation leads to brain activations, which are in large part, similar to those induced by a "neurogenic" stress and that the paraventricular thalamic nucleus is involved in this response. These changes could contribute to the development of hyperphagia and obesity.