Milk composition and milk intake were measured in lean and preobese Zucker rat pups. Lactating dams were injected with 3H2O, which equilibrated with plasma water within 30 minutes. A constant specific activity of 3H was maintained by adding 3H2O to drinking water. Blood samples of 5 microliters were obtained from 1, 15 and 20-day-old suckling pups every 4 hours for a 24-hour period and the accumulation of tritium was used to calculate pups' milk intake. No diurnal variation in milk intake of pups was observed. Obese pups were identified at 5 weeks of age and showed no difference in milk intake compared to lean littermates at 10, 15 and 20 days of age. Milk intake of pups increased with age from 2.0 ml at day 10 to 15.8 ml by day 20. Food and water intake of dams also increased from day 10 to 20 of lactation. The protein and carbohydrate component of rat milk did not change significantly from day 5 to 20 of lactation; however, the fat component decreased significantly from 12.7% at day 5 to 4.2% at day 20.

Treatment of 15-week-old obese and lean mice with the amphetamine derivative fenfluramine (15,25, and 40 mg/kg body wt, ip) for 14 days did not reduce body weight, except in lean mice receiving 40 mg/kg. In vivo insulin sensitivity, measured as the ability of exogenous insulin (1 IUIkg body wt, ip) to lower blood glucose, was improved in obese mice receiving the two higher doses (25 and 40 mg/kg) of fenfluramine for 14 days, when compared to untreated obese mice. There was no change in insulin sensitivity between treated and untreated lean mice. This improvement, seen in obese mice which did not lose weight, demonstrates an effect of this drug distinct from its anorexigenic properties. On Day 21 of fenfluramine treatment, the in vivo rates of fatty acid synthesis were determined by injecting 3 H 2 0 ip and measuring the amount of 3H incorporated into fatty acids over a 1-hr period. The rates of fatty acid synthesis per gram of liver and adipose tissue of obese and lean mice receiving 40 mg/kg fenfluramine were unchanged when compared to sham-injected controls. However, fat depletion was observed in epididymal fat pads of treated (40 mg/kg) lean mice, indicating either reduced lipid deposition or stimulated lipolysis in this group. In vitro, a therapeutic concentration (100 ng/ml) of fenfluramine increased insulin-stimulated conversion of [U-14C]glucose to fatty acids but not CO, and total lipids in isolated adipocytes from lean but not obese mice. These results indicate that the reduction of insulin resistance in obese mice treated with fenfluramine does not influence rates of lipogenesis in liver and adipose tissue but may be associated with increased insulin sensitivity of other tissues such as muscle.24 1 0037-9727181102024 1-08$01 .OO/O