Ventromedial hypothalamic lesions produced by gold thioglucose do not impair induction of NPY mRNA in the arcuate nucleus by fasting

There is increasing evidence that neuropeptide Y (NPY) plays an important role in the regulation of food intake. Neuropeptide Y mRNA in the arcuate nucleus increases after fasting and it has been proposed that this increase in NPY activity occurs as a result of the decreased circulating levels of both insulin and glucose associated with a fast. Glucose-responsive neurons in the ventromedial nucleus (VMN) of the hypothalamus alter their activity in response to changes in circulating glucose levels and these neurons have been proposed to be involved in the regulation of feeding behavior and metabolism. However, it is not known if these glucose-responsive neurons are involved in the response of NPY mRNA in the arcuate nucleus to fasting. To address this relationship, mice were injected with either saline or gold thioglucose (GTG), which appears to act on glucose-responsive neurons, and killed 6 weeks later after a 72 h fast or under ad lib fed conditions. In situ hybridization histochemistry for NPY mRNA was performed on hypothalamic sections containing the arcuate nucleus. The number of labelled cells was counted and the density of autoradiographic silver grains overlying the cells was also quantified (i.e. pixels per cell). Fasting resulted in increased levels of total NPY mRNA (number of labelled cells multiplied by the pixels per cell) in the arcuate nucleus of both control and GTG-treated mice. In addition, the relative fasting-induced increase (i.e. the fasted to fed ratio) in number of cells detected, number of pixels per cell, and total NPY mRNA was similar in both the control and GTG-treated mice. These data suggest that GTG-sensitive VMN neurons play little role in the induction of NPY mRNA by fasting in the arcuate nucleus.