This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acute treatment of humans and rodents with PYY3-36 and PP inhibits food intake for up to 12 hours. When given daily for several days, both of these hormones have been reported to cause continuous decrease in body weight gain in male rats, with no evidence of desensitization. We have recently shown that PYY3-36 (a selective Y2 receptor agonist), given iv, can cause sustained decreases in food intake over 5 days in the NHP, indicating it may be a useful obesity therapy in humans. However, the ability of PP (a selective Y4 receptor agonist) to cause sustained decreases in food intake in the NHP has not been tested. Furthermore, it is hypothesized that a combined treatment with a Y2 and Y4 agonist may cause more potent decreases in food intake and may be a powerful obesity therapy. This study has a simple overriding goal, to determine whether daily infusion of PP and the PYY/PP analogue alters energy homeostasis in macaques. We are confident that both of these peptides will inhibit macaque food intake acutely; however, until we know what the effect of longer-term treatment is, we are unable to evaluate the efficacy of these peptides as a treatment for human obesity. Energy homeostasis has many components: for simplicity we will only evaluate 3 components: food intake, body weight, and adiposity. From these factors we can calculate metabolic efficiency as an estimate of energy expenditure.
The aims of the project are to determine if PP or the PYY/PP analogues cause acute decreases in food intake in nonhuman primates, and if chronic administration of the PP or PYY/PP analogues cause sustained decreases in food intake and weight loss.
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