The antiobesity and metabolic activities of LY79771 in obese and normal mice.

Without affecting the appetite, Compound LY79771 reduced the body weight of obese Avy/a mice, prevented young Avy/a mice from becoming obese and ob/ob mice from becoming overtly obese. This weight-controlling effect of LY79771 was reversible upon withdrawal of treatment. The major portion of the weight change induced by the compound was due to a reduction in triacylglycerol content of the body. Hyperinsulinemia and hyperglycemia of the obese mice were also improved. In spite of its potent lipolytic activity, only a 20 to 25 per cent excess of fatty acid was found in the liver after dosing. No accumulation of fatty acid was observed in the carcass. A single dose of LY79771 also stimulated metabolism as indicated by the increase of CO2 expiration. The transient rise of body temperature that occurred after each injection in a long-term treatment regimen suggested that the compound was thermogenic. LY79771 had no effect on the weight of normal mice.