Central prostaglandin D(2) stimulates food intake via the neuropeptide Y system in mice.

We found that prostaglandin (PG) D(2), the most abundant PG in the central nervous system, stimulates food intake after intracerebroventricular administration in mice. The orexigenic effect of PGD(2) was mimicked by a selective agonist for the DP(1) receptor among two receptor subtypes for PGD(2), and abolished by its antagonist. Central administration of an antagonist or antisense oligodeoxynucleotide for the DP(1) 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 PGD(2) was also abolished by an antagonist for neuropeptide Y (NPY) Y(1) receptor. Taken together, PGD(2) may stimulate food intake through central DP(1) receptor coupled to the NPY system.