Food-entrained rhythmic expression of apolipoprotein E expression in the hypothalamus of rats

Apolipoprotein E (apoE) is a protein mainly synthesized in the liver and brain. To further understand the role of brain apoE in the management of daily food intake, we have examined the circadian pattern of hypothalamic apoE gene and protein expression in freely-fed (FF) and food-restricted (RF, food provided 4 h daily between 1000 h and 1400 h) rats sacrificed at 3-h intervals throughout the light-dark cycle. In FF rats, hypothalamic apoE mRNA and protein levels fluctuated with peaks occuring during the dark phase and the nadirs occuring during the light phase. This pattern was altered in RF rats, which had a marked increase in hypothalamic apoE mRNA and protein levels during the 4-h feeding period in the light phase. Although corticosterone (CORT) levels temporally coincided with the increasing phase of apoE in the hypothalamus in both FF and RF rats, depletion of CORT by adrenalectomy (ADX) did not significantly influence the hypothalamic apoE levels during either period, implying that the circadian pattern of hypothalamic apoE is regulated by factors other than circulating CORT. The finding that hypothalamic apoE and food intake are positively associated during the normal circadian cycle as well as in the period of restricted feeding suggests that hypothalamic apoE is food-entrained and likely involved in the physiological regulation of daily food intake.