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

Abstract

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-1beta. 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-1beta 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.

• Authors: E Pecchi, M Dallaporta, S Thirion, C Salvat, F Berenbaum, A Jean, J-D Troadec
• Journal: Physiological genomics (Physiol Genomics) Vol. 25 Issue 3 Pg. 485-92 (May 16 2006) ISSN: 1531-2267 [Electronic] United States
• PMID: 16554545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• RNA, Messenger
• Cyclooxygenase 2
• Ptgs2 protein, rat
• Intramolecular Oxidoreductases
• Prostaglandin-E Synthases
• Ptges protein, mouse
• Dinoprostone

Topics

• Animals
• Anorexia (chemically induced, enzymology)
• Body Weight (drug effects)
• Cyclooxygenase 2 (genetics, metabolism)
• Dinoprostone (toxicity)
• Eating (drug effects)
• Hypothalamus (drug effects, enzymology)
• Injections, Intraperitoneal
• Injections, Intraventricular
• Interleukin-1beta (administration & dosage, toxicity)
• Intramolecular Oxidoreductases (genetics, metabolism)
• Male
• Mice
• Mice, Inbred DBA
• Mice, Knockout
• Prostaglandin-E Synthases
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Time Factors
• Up-Regulation
• Vagus Nerve (drug effects, enzymology)