Differential suppression of hyperglycemic, feeding, and neuroendocrine responses in anorexia

Abstract

We have used the anorexia shown by rats given hypertonic saline to drink to investigate central mechanisms that can inhibit feeding. Rats dehydrated in this manner for 3 or 5 days showed a severe attenuation of the compensatory feeding observed after an overnight fast compared with control euhydrated rats or rats whose food was restricted to match the intake of anorexic rats. Food intake after injections of 2-deoxy-d-glucose (2-DG) was also significantly decreased in dehydrated animals compared with that after a 2-DG injection given before dehydration. However, all the dehydrated animals demonstrated a robust eating response after water was returned whether they had received injection of 2-DG or vehicle. Despite a profound reduction in 2-DG-induced feeding, other glucoregulatory responses to 2-DG remained intact in dehydrated animals. After 2-DG injection, corticosterone secretion and blood glucose were significantly elevated from preinjection values whether or not animals were dehydrated. Thus the mechanisms responsible for anorexia in dehydrated animals specifically target stimulatory feeding pathways but leave intact other counterregulatory glucometabolic motor events.

Neural network interactions and ingestive behavior control during anorexia

“…Within this model, our data show that dehydration targets PVH neurons more effectively than LHA neurons to suppress feeding. Combined with the results from our 2DG experiments [30], our NPY data suggest that one reason that 2DG feeding is suppressed is because the sensitivity to the NPY colocalized within adrenergic inputs to the PVH is diminished by DE. Furthermore, a desensitization of NPY mechanisms in the PVH and LHA may explain why dehydrated animals have a reduced feeding response to overnight starvation [30], which is an NPY-dependent mechanism [33,34].…”

“…In this way, NPY-sensitive targets in the LHA and particularly the PVH, are actively suppressed during dehydration-anorexia. This suppression may also be sufficient to account for the reduced feeding we have previously reported following overnight starvation or 2DG injections [30]. Furthermore, the feeding that follows inhibition of the ACBsh is suppressed by DE, showing that the downstream targets of the ACBsh are also affected.…”

“…Furthermore, the fact that dehydration suppresses feeding but not the glucocorticoid response to 2DG-both of which require ascending catecholaminergic projections to the PVH [22]-clearly demonstrates that ascending catecholaminergic afferents remain functionally intact during dehydration-anorexia. The fact the dehydration differentially targets control elements in the PVH for feeding and neuroendocrine CRH release-suppressing one but not the other [30]shows that the effects of dehydration within the PVH are exquisitely site specific.…”

“…In animals dehydrated by drinking 2.5% hypertonic saline for 5 days only the feeding response to 2DG is suppressed. In these same animals, the hyperglycemic and plasma corticosterone responses remain intact (Data adapted from [30]) The difference between the 4 hour feeding response of individual animals injected with 1μg of neuropeptide Y in the lateral hypothalamic area in the euhydrated state and then injected again later in the dehydrated state (after drinking 2.5% hypertonic saline). The data show that the suppression of NPY-induced feeding is inversely correlated to the intensity of the anorexia that develops as a consequence of dehydration (Data adapted from [32]).…”

“…To investigate how these viscerosensory relay systems are impacted during dehydrationanorexia, we determined how animals responded to intravenous injections of 2DG [30]. Ordinarily 2DG will stimulate feeding, ACTH release, and hyperglycemia.…”