Showing papers by "Harvey J. Grill published in 2005"
TL;DR: It is concluded that the inhibitory signals mediating postprandial ghrelin suppression are not derived discretely from either the stomach or duodenum, and the relatively weak suppression of gh Relin by lipids compared with glucose or amino acids could represent one mechanism promoting high-fat dietary weight gain.
Abstract: The orexigenic hormone ghrelin is implicated in preprandial hunger and meal initiation in part because circulating levels increase before meals and decrease after food intake. The mechanisms underlying postprandial ghrelin suppression are unknown. Although most ghrelin is produced by the stomach, we have shown that neither gastric nutrients nor gastric distension affect ghrelin levels. We hypothesized that the nutrient-sensing mechanism regulating ghrelin is in the duodenum, the second richest source of ghrelin. To test whether duodenal nutrient exposure is required for ghrelin suppression, we infused nutrients into either the proximal duodenum or proximal jejunum in rats bearing chronic intestinal cannulas. At 0, 30, 60, 90, 120, 180, 240, and 300 min after infusions, blood was sampled via jugular-vein catheters for ghrelin, insulin, and glucose measurements. To elucidate further the mechanisms governing nutrient-related ghrelin suppression, we also assessed the ghrelin responses to isocaloric (3 kcal) i...
202 citations
TL;DR: Different mediating pathways are demonstrated for the hyperphagic response driven separately by forebrain and CBS ghrelin administration and preadministration of either of the two antagonists through the same cannula reversed the hyperPHagic response.
Abstract: Neuropeptide Y (NPY) has been implicated in the downstream mediation of ghrelin hyperphagia, with the site of action for both peptides considered to be intrinsic to the hypothalamus. Here, however, we observed robust hyperphagia with caudal brainstem (CBS) (fourth intracerebroventricular) ghrelin delivery and, moreover, that this response was reversed with coadministration of either of two NPY receptor antagonists (1229U91 and D-Tyr27,36, D-Thr32 NPY27-36) with contrasting NPY receptor subtype-binding properties. The same results were obtained after forebrain (third intracerebroventricular) administration, but the sites for both ghrelin and antagonist action were open to question, given the caudal flow of cerebrospinal fluid (CSF) through the ventricular system. To control for this, we occluded the cerebral aqueduct to restrict CSF flow between the forebrain and CBS ventricles and tested all combinations (same and cross ventricle) of ghrelin (150 pmol/1 microl) and NPY receptor antagonist delivery. With fourth intracerebroventricular ghrelin delivery after aqueduct occlusion, preadministration of either of the two antagonists through the same cannula reversed the hyperphagic response but neither was effective when delivered to the third ventricle. With third intracerebroventricular ghrelin administration, however, 1229U91 reversed the ingestive response only when delivered to the fourth ventricle, whereas D-Tyr27,36) D-Thr32 NPY27-36 was effective only when delivered to the forebrain. These results demonstrate distinct mediating pathways (due to location and subtypes of relevant NPY receptor) for the hyperphagic response driven separately by forebrain and CBS ghrelin administration.
50 citations