Complement C5a stimulates food intake via a prostaglandin D2- and neuropeptide Y-dependent mechanism in mice

We have recently found that prostaglandin (PG) D2 stimulates food intake via DP1 receptor. Here we show that complement C5a stimulates food intake by activating the orexigenic PGD2 system. C5a (30–100 pmol/mouse), after intracerebroventricular administration, stimulated food intake in non-food-deprived mice. The orexigenic activity of C5a was blocked by co-administration of a DP1 receptor antagonist, BWA868C. Central administration of C5a elevated the hypothalamic mRNA expression of COX-2 but not COX-1, and the food intake stimulation of C5a was inhibited by pretreatment with a COX-2 inhibitor, celecoxib, suggesting that C5a activates COX-2 upstream of the PGD2–DP1 system. The orexigenic activity of C5a was also inhibited by an antagonist for neuropeptide Y (NPY) Y1 receptor, which was activated downstream of the PGD2–DP1 system. These results suggest that C5a stimulates food intake via a PGD2- and NPY-dependent mechanism. C5a is the first example of orexigenic peptides acting through the PGD2–NPY system in the central nervous system.