Gadolinium chloride pretreatment prevents cafeteria diet-induced sleep in rats.

The liver Kupffer cells constitute the largest population of fixed macrophages in the body and reside at a strategic position in liver sinusoids to interact with mediators from the gut. Previously, we showed that cafeteria feeding increases sleep by a subdiaphragmatic mechanism and increases interleukin-1beta (IL-1beta) mRNA expression in rat liver and brain. Thus, the aim of the present experiment was to test the hypothesis that macrophages, in particular liver Kupffer cells, contribute to the excess sleep observed in cafeteria diet fed rats. Sleep-wake activity and brain temperature (T(br)) were examined in rats injected with gadolinium chloride (GdCl3) alone and in rats fed a cafeteria diet with or without prior pretreatment with GdCl3. The intravenous administration of GdCl3 alone, using a dose that blocks phagocytosis and eliminates large Kupffer cells (7.5 mg/kg), increased sleep in the dark period of the light-dark cycle and decreased sleep in the light period. Sleep-wake activity returned to baseline levels 24 h after the injection. In control rats, cafeteria feeding increased non-rapid eye movement sleep (NREMS) and T(br), and decreased rapid eye movement sleep (REMS) and electroencephalographic slow-wave activity (SWA) during NREMS. GdCl3 pretreatment prevented the increase in NREMS, but did not significantly affect REMS, T(br), or SWA during NREMS compared with the control rats. These results suggest that liver Kupffer cells contribute to the excess NREMS that accompanies increased feeding possibly via their capacity to produce IL-1beta.