Significance There is experimental evidence that _-adrenergic adrenergic receptors are involved in the regulation of energy expenditure. Therefore, _-3 adrenergic agonists have therapeutic potential in the treatment of obesity and type-2 diabetes. Objectives We will be examining the effects of a novel _-3-agonist compound developed by Asahi Pharmaceutical. Asahi Pharmaceutical previously tested the safety of the compound in rodents. We determined the effects of the drug on resting metabolic rate (RMR) and plasma levels of insulin, glucose, and free fatty acids (FFAs) in male rhesus monkeys. Results The effects of the compound were examined in two non-obese rhesus monkeys. The order of the study with the Asahi compound and with the placebo study was alternated in the two animals. There was 1 week interval between studies. For the RMR study, animals were fasted overnight and brought to the CRPRC exposure facility in the morning. The animals were previously acclimated to the testing chambers. Each animal had a baseline RMR measurement (indirect calorimetry by oxygen consumption). Then the Asahi compound or a placebo was administered orally and RMR was continuously measured for 6 hours. To examine the effects of the compound on plasma insulin, glucose, and FFAs, the animals were fasted overnight. Two baseline blood samples were collected by venipuncture 15 minutes apart. Then the Asahi compound or a placebo was administered orally. Blood samples were taken at 0.5, 1, 2, 4, 6, and 12 hours after the drug or placebo was administered and analyzed for insulin, glucose, and FFAs in Dr. Havel's laboratory in the Department of Nutrition. The experiments have been completed and the results are currently being analyzed. Future Directions We are planning to use the rhesus monkey model (both normal weight and obese animals) to examine the effects of other Asahi _-3 agonists as they are developed. KEY WORDS _-3 adrenergic, obesity, diabetes, resting metabolic rate, insulin, glucose, free fatty acids FUNDING Asahi Chemical Co, Ltd. Shizuoka, Japan
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