Pecchi E, Dallaporta M, Thirion S, Salvat C, Berenbaum F, Jean A, Troadec J-D
Laboratoire de Physiologie Neurovégétative, UMR 6153 Centre National de la Recherche Scientifique-1147 Institut National de la Recherche Agronomique, Université Paul Cézanne, Marseille, France.
Physiol Genomics. 2006 May 16;25(3):485-92. doi: 10.1152/physiolgenomics.00306.2005. Epub 2006 Mar 22.
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.
作为对感染或炎症的反应，个体出现一组被称为疾病行为的症状，其中包括食物摄入量减少。阐明这种食欲减退背后的分子机制仍然至关重要，因为慢性厌食可能构成重大健康风险。前列腺素（PGs）是一个重要的炎症介质家族，其水平在炎症状态下会在大脑中升高，并且有人提出它们参与炎症诱导的厌食。微粒体PGE合酶（mPGES）-1酶参与PGE2生物合成的最后一步，其表达受到促炎剂的刺激。本研究试图确定mPGES-1基因表达的上调是否可以解释免疫诱导的厌食行为。我们将研究重点放在下丘脑和迷走神经背核复合体中mPGES-1的表达上，这两个结构在周围炎症期间会被强烈激活并参与食物摄入的调节。我们发现，在腹腔内和脑室内注射致厌食剂量的IL-1β后，这些结构中的mPGES-1基因表达被强烈上调。这种增加与厌食的开始相关。食物摄入量的同时减少和中枢mPGES-1基因的上调促使我们测试炎症期间缺乏mPGES-1的小鼠的进食行为。有趣的是，IL-1β未能降低mPGES-1（-/-）小鼠的食物摄入量，尽管这些动物在注射PGE2后会出现厌食。综上所述，我们的结果表明，在参与进食控制的中枢结构炎症期间强烈上调的mPGES-1对于免疫性厌食行为至关重要，因此可能构成一个潜在的治疗靶点。
