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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17870

Title: Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality.
Authors: Teoh, H
Quan, A
Bang, KWA
Wang, G
Lovren, F
Vu, V
Haitsma, JJ
Szmitko, PE
Al-Omran, M
Wang, CH
Gupta, M
Peterson, MD
Zhang, H
Chan, L
Freedman, J
Sweeney, G
Verma, S
Department: Physiology
St. Michael's Hospital
Keywords: adipokine
neutrophil recruitment
cytokines
Issue Date: Sep-2008
Publisher: American journal of physiology. Endocrinology and metabolism
Citation: Teoh H et al. Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality. Am J Physiol Endocrinol Metab. 2008;295(3):E658-64.
Abstract: Sepsis is a multifactorial, and often fatal, disorder typically characterized by widespread inflammation and immune activation with resultant endothelial activation. In the present study, we postulated that the adipokine adiponectin serves as a critical modulator of survival and endothelial activation in sepsis. To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice, subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in survival compared with their wild-type Adipoq(+/+) littermates after 48 h. Furthermore, compared with wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were blunted by recombinant total adiponectin administration given 3 days prior to thioglycollate challenge. The protective effects of adiponectin were ascribed largely to higher-order adiponectin oligomers, since administration of recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and a potential mechanistic link between adiposity and increased sepsis.
URI: http://hdl.handle.net/1807/17870
ISSN: 1522-1555
Appears in Collections:Faculty Publications

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