Diurnal rhythm of apolipoprotein A-IV in rat hypothalamus and its relation to food intake and corticosterone.

Apolipoprotein A-IV (apo A-IV) is a satiety protein synthesized in the small intestine and hypothalamus. To further understand the roles of central apo A-IV in the management of daily food intake, we have examined the diurnal patterns of hypothalamic apo A-IV gene and protein expression in freely feeding and food-restricted (food provided 4 h daily between 1000 h and 1400 h) rats. In freely feeding rats, the hypothalamic apo A-IV mRNA and protein levels fluctuated, with high levels during the light phase, peaking at 0900 h (3 h after lights on), and low levels during the dark phase, with a nadir at 2100 h (3 h after lights off). The daily patterns of the fluctuation, however, were altered in food-restricted rats, which had a marked decrease in hypothalamic apo A-IV mRNA and protein levels during the 4 h-feeding period of the light phase. Although corticosterone (CORT) secretion temporally coincided with the decreasing phase of apo A-IV in the hypothalamus, depletion of CORT by adrenalectomy significantly decreased, rather than increased, hypothalamic apo A-IV mRNA and protein levels. These results indicate that the diurnal expression of hypothalamic apo A-IV is regulated by factors other than the circulating CORT, for example, the reduced food intake and body weight in adrenalectomized animals. The fact that hypothalamic apo A-IV level and food intake were inversely related during the normal diurnal cycle as well as in the period of restricted feeding suggests that hypothalamic apo A-IV is involved in the regulation of daily food intake.