Central prostaglandin D2 stimulates food intake via the neuropeptide Y system in mice

We found that prostaglandin (PG) D2, the most abundant PG in the central nervous system, stimulates food intake after intracerebroventricular administration in mice. The orexigenic effect of PGD2 was mimicked by a selective agonist for the DP1 receptor among two receptor subtypes for PGD2, and abolished by its antagonist. Central administration of an antagonist or antisense oligodeoxynucleotide for the DP1 receptor remarkably decreased food intake, body weight and fat mass. Hypothalamic mRNA levels of lipocalin-type PGD synthase were up-regulated after fasting. The orexigenic activity of PGD2 was also abolished by an antagonist for neuropeptide Y (NPY) Y1 receptor. Taken together, PGD2 may stimulate food intake through central DP1 receptor coupled to the NPY system.