Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality

Am J Physiol Endocrinol Metab. 2008 Sep;295(3):E658-64. doi: 10.1152/ajpendo.90384.2008. Epub 2008 Jul 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / deficiency*
  • Adiponectin / genetics
  • Adiponectin / pharmacology
  • Animals
  • Cecum / physiology
  • Cytokines / biosynthesis
  • Endothelium / physiology*
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Intestinal Perforation / pathology
  • Leukocyte Count
  • Ligation
  • Mice
  • Mice, Knockout
  • Peritonitis / pathology
  • Recombinant Proteins / pharmacology
  • Sepsis / genetics
  • Sepsis / mortality*
  • Sepsis / physiopathology*
  • Survival Analysis
  • Thioglycolates


  • Adiponectin
  • Cytokines
  • Recombinant Proteins
  • Thioglycolates