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Involvement of central microsomal prostaglandin E synthase-1 in IL-1ß-induced anorexia

¹ Laboratoire de Physiologie Neurovégétative, UMR 6153 Centre National de la Recherche Scientifique (CNRS)-1147 Institut National de la Recherche Agronomique (INRA), Université Paul Cézanne, Marseille
² Laboratoire de Physiologie et Physiopathologie, UMR 7079 CNRS, Université Pierre et Marie Curie, Paris
³ Laboratoire des Interactions Cellulaires Neuroendocriniennes, UMR 6544 CNRS, Université de la Méditerranée, Marseille, France

In response to infection or inflammation, individuals develop a set of symptoms referred to as sickness behavior, which includes a decrease in food intake. The characterization of the molecular mechanisms underlying this hypophagia remains critical, because chronic anorexia may represent a significant health risk. Prostaglandins (PGs) constitute an important inflammatory mediator family whose levels increase in the brain during inflammatory states, and their involvement in inflammatory-induced anorexia has been proposed. The microsomal PGE synthase (mPGES)-1 enzyme is involved in the last step of PGE₂ biosynthesis, and its expression is stimulated by proinflammatory agents. The present study attempted to determine whether an upregulation of mPGES-1 gene expression may account for the immune-induced anorexic behavior. We focused our study on mPGES-1 expression in the hypothalamus and dorsal vagal complex, two structures strongly activated during peripheral inflammation and involved in the regulation of food intake. We showed that mPGES-1 gene expression was robustly upregulated in these structures after intraperitoneal and intracerebroventricular injections of anorexigenic doses of IL-1ß. This increase was correlated with the onset of anorexia. The concomitant reduction in food intake and central mPGES-1 gene upregulation led us to test the feeding behavior of mice lacking mPGES-1 during inflammation. Interestingly, IL-1ß failed to decrease food intake in mPGES-1^–/– mice, although these animals developed anorexia in response to a PGE₂ injection. Taken together, our results demonstrate that mPGES-1, which is strongly upregulated during inflammation in central structures involved in feeding control, is essential for immune anorexic behavior and thus may constitute a potential therapeutic target.

inflammation; interleukin-1ß; cyclooxygenase; prostaglandin E₂

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