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  4. Hyperphagia and obesity results from the injection of the immunotoxin neuropeptide Y (NPY)-saporin (NPY-sap) into the paraventricular hypothalamus (PVH) of rats.

Hyperphagia and obesity results from the injection of the immunotoxin neuropeptide Y (NPY)-saporin (NPY-sap) into the paraventricular hypothalamus (PVH) of rats.

Bugarith K, Ritter S, Dinh T (2001) Hyperphagia and obesity results from the injection of the immunotoxin neuropeptide Y (NPY)-saporin (NPY-sap) into the paraventricular hypothalamus (PVH) of rats. Neuroscience 2001 Abstracts 948.2. Society for Neuroscience, San Diego, CA.

Summary: NPY is a peptide implicated in the control of numerous physiological processes. A variety of G-protein coupled receptors, Y1, Y2, Y4, and Y5, mediate the actions of NPY. Recently a new immunotoxin, NPY-SAP, has been developed that is potentially of great importance for the study of NPY function. NPY-SAP is a conjugate of the peptide NPY and saporin, a plant toxin that inactivates ribosomes. The proposed mechanism of toxicity involves immunotoxin binding NPY receptors and destruction of neurons containing these receptors. In this study we injected different doses of NPY-sap or unconjugated saporin (SAP) into the PVH to test the effects of this new toxin. We found that at low doses, there was no effect of NPY-SAP on cytoarchitecture or immunoreactivity of select peptides in the PVH. There was also no difference in body weight between the groups. At high doses, there was histologically-detectable damage in the hypothalamus of NPY-SAP animals. We also found a major difference in body weight between the NPY-SAP rats and SAP controls. Ten weeks after the injections, the NPY-SAP rats (654.3g ± 39.04g) were much heavier than the SAP rats (410.6g ± 15.29g). Further, daytime (0800 – 1700H) food intake was about twice as much in NPY-SAP (9.53g ± 0.996g) as in SAP (5.74g ± 0.476g) rats, with no difference in overnight (1700 – 0800H) feeding. Work is ongoing to determine the specificity of the lesion and the mechanism of action of NPY-SAP.

Related Products: NPY-SAP (Cat. #IT-28)

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