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Diurnal Rhythm of Apolipoprotein A-IV in Rat Hypothalamus and Its Relation to Food Intake and Corticosterone

Cincinnati Obesity Research Center (M.L., R.S., S.C.W., P.T.), Department of Pathology and Laboratory Medicine (M.L., L.S., Y.L., D.T., P.T.), Department of Psychiatry (R.S., S.C.W.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

Address all correspondence and requests for reprints to: Min Liu, Ph.D., Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0507. E-mail: lium{at}uc.edu.

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.

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