Continuous intravenous infusion of ghrelin does not stimulate feeding in tumor-bearing rats.

The development of anorexia continues to be a serious treatment issue for cancer patients. Because the orexigenic peptide, ghrelin, is active through systemic routes and activates hypothalamic neuropeptide systems known to be refractory in anorectic tumor-bearing (TB) rats, we investigated whether it would prevent the development of cancer anorexia when infused continuously intravenously. The 24-h food intake was increased in nontumor-bearing (NTB) rats at a dose of 288 microg/day ghrelin.

Alteration of NPY and Y1 receptor in dorsomedial and ventromedial areas of hypothalamus in anorectic tumor-bearing rats.

Although previous studies have implicated NPY in the etiology of experimental cancer anorexia, the results have been difficult to interpret. Studies have suggested that although NPY level and message were decreased in the dorsomedial hypothalamic area (DMA), they were elevated in the ventromedial hypothalamic area (VMA). To better assess specific intra-area alterations of NPY, Y(1) receptor (Y(1) R), and agouti-related peptide (AgRP) in TB rats, we used radioimmunoassay, quantitative real-time RT-PCR, and immunohistochemistry.

Mediation of burn-induced hypermetabolism by CRF receptor-2 activity.

Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have implicated hypothalamic peptides and receptors of the corticotropin releasing factor (CRF) family as putative mediators of burn-induced hypermetabolism. Increased neuronal activity at the CRF type 2 receptor (CRF R-2) appeared particularly involved in the expression of elevated resting energy expenditure (REE) following major burn trauma.

The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut hypoplasia.

Total parenteral nutrition (TPN) of rats has been demonstrated to produce hypoplasia of gut mucosa, and to be associated with reduced immune response and elevated translocation of bacteria from gut to mesenteric lymph nodes, spleen and liver. Treatment of rats being maintained on TPN with the proglucagon fragment, glucagon-like peptide-2 (GLP-2), has been shown to totally prevent small intestine mucosal hypoplasia. In the present study, we found that depletion of polyamines with alpha-difluromethylornithine (DFMO) significantly reduced the efficacy of GLP-2 in preserving gut mucosa in rats maintained on TPN for 8 days.

Possible role of CRF peptides in burn-induced hypermetabolism.

Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have shown that hypothalamic corticotropin releasing factor (CRF) elevates metabolic rate, while neuropeptide Y (NPY) reduces it. CRF also elicits anorexia, while NPY stimulates feeding.

Elevated blood lactate is not a primary cause of anorexia in tumor-bearing rats.

Tumor-bearing (TB) rats exhibit elevated concentrations of lactate in blood contiguous with the development of anorexia. Continuous intravenous infusion of lactate into non-TB rats reduced food intake at plasma concentrations lower than those observed in anorectic TB rats. Levels of neuropeptide Y (NPY) were elevated in the ventromedial (VMH) and dorsomedial hypothalamic regions of lactate-infused rats.