CHRONIC ADMINISTRATION OF OB PROTEIN DECREASES FOOD-INTAKE BY SELECTIVELY REDUCING MEAL SIZE IN MALE RATS

The potent hypophagic effect of OB protein (OB) is well established, b ut the mechanism of this effect is largely unknown. We investigated th e effects of chronic administration of a novel modified recombinant hu man OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male S prague-Dawley rats (body weight at study onset: 292 g). Single daily s ubcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive day s significantly reduced ad libitum food intake compared with vehicle i njections from injection day 3 through postinjection day 3. Mod-OB-inj ected rats ate between 4.5 and 7.1 g(or 13-20%) per day less than cont rols, with the reduction primarily occurring during the dark period. B ody weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal siz e. There was no significant effect of Mod-OB on nocturnal meal frequen cy or duration. Mod-OB also did not reliably affect the size, duration , or frequency of diurnal meals. Mod-OB-injected rats displayed no com pensatory hyperphagia after the injection period. These results indica te that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.