Adiponectin, a key substance in metabolic syndrome, is known to have anti-inflammatory properties. The relationship between adiponectin and sepsis in vivo is unclear. In this study, the possible involvement of adiponectin in polymicrobial sepsis was investigated using adiponectin-knockout (APN-KO) mice that underwent cecal ligation and puncture (CLP) and received the peroxisome proliferator-activated receptor gamma (PPAR-γ) that increases the plasma adiponectin concentration.
Methods
APN-KO and wild-type (WT) mice underwent either CLP or a sham operation. The plasma adiponectin, endotoxin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were determined before and at 2, 4, 6, 8, 12, 16, and 24 hours after the procedures, and the survival rates were compared. Mice were injected with rosiglitazone, a selective PPAR-γ agonist, and compared survival rates after CLP with those without rosiglitazone.
Results
After CLP, APN-KO mice had a significantly higher mortality than WT mice. The plasma endotoxin, TNF-α, and IL-6 levels in APN-KO mice were significantly higher than those in WT mice 24 hours after CLP. Within 4 hours after CLP, the plasma adiponectin level in WT mice decreased to half of the initial levels. Pre-CLP treatment with PPAR-γ was shown to increase the plasma adiponectin level and to improve significantly mortality of WT mice during sepsis; mortality among APN-KO mice did not improve.
Conclusion
These results suggest that adiponectin deficiency may cause the high mortality and the high inflammatory cytokine levels in mice with polymicrobial sepsis.
aDepartment of Surgery, Shiga University of Medical Science, Shiga, Japan
bDepartment of Metabolic Medicine, Graduate School of Osaka University, Osaka, Japan
Reprint requests: Hiroshi Yamamoto, MD, PhD, Department of Surgery, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Y.U., H.T., T.S., and Y.E. contributed equally to this manuscript.
ABSTRACT