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Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice

Department of Kinesiology and Nutrition (M.P., M.E.G., J.A.S., J.W.P.M.v.B., G.F.), University of Illinois at Chicago, Chicago, Illinois 60612; and Department of Molecular and Cellular Biology (L.C.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Giamila Fantuzzi, University of Illinois at Chicago, 1919 West Taylor Street MC 517, Chicago, Illinois 60612. E-mail: giamila{at}uic.edu.

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNF, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNF, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

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