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To minimize the postprandial elevation of fuels, animals make a series of adaptive physiological responses in anticipation of eating large meals. These cephalic responses are especially prominent when animals are meal-fed (MF), consuming all of their daily food in a 4-hr window. We have reported previously that MF rats have anticipatory secretion of insulin and ghrelin preceding their expected meals. More recently we have noted that MF animals have improved glucose tolerance at the time food is anticipated. However, because MF is associated with a small but significant weight decrement compared with ad lib-fed controls, specific beneficial effects of meal feeding cannot easily be dissociated from effects of reduced body mass. To control for body weight effects on glucose tolerance during the MF paradigm, male rats were placed on 1 of 3 feeding schedules for 14 days. The control (al lib) group had free access to chow at all times. The MF group had free access to chow from 1000 to 1400 hrs each day. The snack (S) group also had ad lib chow, and additionally had 30-min access to Ensure each day from 1000 to 1030 hrs. After 14 days, all rats were fasted for 20 hr and had a meal tolerance test with 5 ml Ensure presented at 1000 hrs. There was a significant effect of feeding schedule on AUC (p< 0.001). MF rots were significantly lighter and leaner and had a 69% decrease in the postprandial increment in blood glucose compared to ad lib controls. S rats had increased body fat and comparable body weight as controls, but had improved meal tolerance with a 27% reduction in the postprandial glycemic response. The ad lib controls were next placed on the S feeding schedule for 2 weeks, followed by a second Ensure tolerance test. This resulted in improved glucose tolerance (12% reduction in AUC, p< 0.058), despite that the rats were now substantially older, heavier and fatter compared to their initial test. These data demonstrate an important effect of scheduled feeding to minimize postprandial hyperglycemia, even in animals that are not food deprived and have elevated body fat. [ABSTRACT FROM AUTHOR]