LONG-TERM EFFECTS OF PYY 3-36 ON RHESUS MACAQUE ENERGY HOMEOSTASIS

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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. Obesity is one of the major health challenges facing the developed world, significantly increasing the risk of coronary disease, and of diabetes. It has recently been shown that for every "point" by which a person's body mass index (BMI) exceeds 25, there is an associated increase (5% in men and 7% in women) in the risk of cardiac disease. Beyond the terrible human costs there are significant economic costs associated with health care for such an obese population. An estimated 9.4% of US healthcare expenditure is directly related to "obesity and inactivity," while recent costs due to diabetes were estimated at $98 billion per annum. In recent years tremendous advances have been made identifying genes and pathways important for regulating energy homeostasis, in particular the hormone-receptor pair leptin (Lepob) and leptin receptor (Lepr, LR). White adipose cells produce leptin and absence of leptin or functional leptin receptors causes morbid obesity. Unfortunately, leptin has not been an effective treatment for most human obesity. Peptide YY (PYY) is secreted by the gut following a meal in proportion to ingested calories, and is constitutively cleaved to PYY3-36. We have recently demonstrated that PYY3-36 inhibits food intake when administered to rodents and humans. We have also demonstrated that daily intraperitoneal injections of PYY3-36 causes sustained inhibition of food intake and significant weight loss in rats. It is crucial to determine if a similar effect is seen in nonhuman primates before we begin testing the effects of long-term PYY3-36 treatment on human adiposity. In collaboration with Dr. Judy Cameron and Dr. Frank Koegler, we are ideally positioned to test the effects of medium-term treatment with PYY 3-36 on rhesus macaque adiposity. If these experiments show the expected decrease in food intake and body fat, it will accelerate the development of PYY 3-36 as a therapeutic agent for the treatment of human obesity.