Metabolic inhibition increases feeding and brain Fos-like immunoreactivity as a function of diet

Whether administration of 2,5-anhydro-D-mannitol (2,5-AM) or methyl palmoxirate (MP) elicits eating behavior in rats depends on the composition of the maintenance diet. To assess whether specific brain sites are involved in triggering the eating responses to these metabolic inhibitors, we measured food intake and Fos-like immunoreactivity (Fos-li) in rats maintained on either a low-fat/high-carbohydrate (LF/HC) or high-fat/low-carbohydrate (HF/LC) diet. Rats fed the LF/HC diet increased food intake after administration of 2,5-AM (200 mg/kg ip) but not after treatment with MP (10 mg/kg po), whereas rats maintained on the HF/LC diet increased food intake in response to MP administration but not after 2,5-AM injection. The effects of these inhibitors on brain Fos-li in several specific brain nuclei paralleled those on feeding behavior; that is, the number of cells showing Fos-li increased only under dietary conditions in which 2,5-AM or MP stimulated eating. These results suggest that the eating response to metabolic inhibition is tied to increased neuronal activity in brain regions that process vagal afferent signals.