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The orexigenic effect of PGD<jats:sub>2<\/jats:sub> was mimicked by a selective agonist for the DP<jats:sub>1<\/jats:sub> receptor among two receptor subtypes for PGD<jats:sub>2<\/jats:sub>, and abolished by its antagonist. Central administration of an antagonist or antisense oligodeoxynucleotide for the DP<jats:sub>1<\/jats:sub> receptor remarkably decreased food intake, body weight and fat mass. Hypothalamic mRNA levels of lipocalin\u2010type PGD synthase were up\u2010regulated after fasting. The orexigenic activity of PGD<jats:sub>2<\/jats:sub> was also abolished by an antagonist for neuropeptide Y (NPY) Y<jats:sub>1<\/jats:sub> receptor. 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