Enhanced food-anticipatory circadian rhythms in the genetically obese Zucker rat

This study examines the effects of the leptin receptor mutation in obese Zucker rats on entrainment of food-anticipatory rhythms to daily feeding schedules. Leptin is secreted by adipocytes in proportion to fat content, exhibits a daily rhythm in plasma that is synchronized to feeding time, and inhibits activity of arcuate neuropeptide Y neurons that stimulate feeding behavior and regulate metabolism. Activity within this neuropeptide Y system is enhanced by food deprivation and attenuated by overfeeding and diet-induced obesity. Diet-induced obesity, in turn, attenuates food-anticipatory rhythms. If the effects of obesity on food-entrained rhythms are mediated by leptin inhibition of neuropeptide Y neurons, then these rhythms may be enhanced in leptin-insensitive Zucker obese rats. Alternatively, if daily rhythms of leptin mediate the generation or entrainment of these rhythms, Zucker rats may fail to anticipate daily feedings. Zucker obese and lean rats received food for 3 h/day during the midlight period. Both groups exhibited significant food-anticipatory activity that persisted during three cycles of food deprivation, but this rhythm was significantly more robust in obese rats, when expressed as anticipation and persistence ratios, and as peak values. Anticipatory rhythms did not persist in either group when food was provided ad lib. These results indicate that central actions of leptin may mediate the inhibitory effects of obesity on the expression of food-anticipatory rhythms in rats, but do not mediate the inhibitory effects of ad lib food access, and do not serve as necessary internal entrainment cues or clock components for the food-entrainable circadian system.