Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C89

Oral Communications

Cholecystokinin participates in the LPS-induced hypophagia through corticotrophin-releasing-factor neuron activation.

R. C. Rorato1, J. Antunes-Rodrigues1, L. L. Elias1

1. Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.


Administration of lipopolyssacharide (LPS) decreases food intake. However, the mechanisms underling this hypophagic effect are not well established. LPS increases peripheral production of cytokines that in turn induce cholecystokinin (CCK) secretion, a satiety-related peptide. CCK induces an activation of brainstem neurons that show reciprocal projections with hypothalamic neurons. Corticotrophin-releasing-factor (CRF) and alpha-melanocyte stimulating hormone (α-MSH) are neuropeptides with anorexigenic properties. This study aimed to investigate the effects of LPS on food intake, CRF and α-MSH neuron activation in rats pretreated with devazepide (CCK-1 receptor antagonist). Adult male Wistar rats (220-300g) were singly housed in metabolic cages with free access to chow offered in a metal container, to verify food consumption. On the day of the experiment the chow were removed and rats(n=7-11) were weighed and pretreated with devazepide (1mg/Kg, ip) or vehicle (0.5/0.5/9, tween80/DMSO/saline0.9%) 30 minutes before LPS (100μg/Kg, ip) or saline (0.1ml/100g bw, ip) injection. Thereafter, food was offered for 2h (18:00-20:00h). Another set of rats (n=5-7) was pretreated with devazepide or vehicle followed by LPS or saline injection and 4h after they were anaesthetized with tribromoethanol (1ml/100g bw, ip) and transcardially perfused with s 4% paraformaldehyde for brain collection. In rats saline injected, devazepide (3.85±0.9 g/100g; p<0.01) increased food intake compared to group pretreated with vehicle (2.89±0.4 g/100g). Food intake was decreased after LPS in vehicle (1.1±0.6 g/100g; p<0.001) pretreated animals, which was reversed by devazepide (2.2±0.9; p=0.06) pretreatment. Devazepide and vehicle pretreatement in saline rats resulted in similar immunoreactivity to Fos/α-MSH (devazepide; 0.5±0.5 and vehicle 0.7±0.9) in the ARC and Fos/CRF in the medial (PaMP; devazepide 4.2±2.4 and vehicle 4.3±1.1) and posterior parvocellular subdivisions of the PVN (PaPo; devazepide 3.2±1.6 and vehicle 3.8±1.4). In the group pretreated with vehicle, LPS treatment increased Fos/CRF double labeled neurons in the PaMP (22.9±6.4; p<0.001) and PaPo (9.1±1.6; p<0.001). No change in the Fos/α-MSH double labeled neurons in the ARC was observed after LPS stimulus (devazepide 0.3±0.7 and vehicle 0.3±0.7). Pretreatment with devazepide decreased the LPS-induced Fos/CRF double labeling in the PaMP (9.5±3.6; p<0.001) and PaPo (4.8±5.5; p<0.001). The present data suggest that CCK participates in the hypophagic effect during endotoxemia through CCK-1 receptor. This effect is likely to be mediated by an activation of CRF neurons in the PVN but not α-MSH in the ARC.

Where applicable, experiments conform with Society ethical requirements