Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality.
BACKGROUND
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-gamma) 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-alpha), 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-gamma 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-alpha, 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-gamma 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.


CONCLUSIONS
These results suggest that adiponectin deficiency may cause the high mortality and the high inflammatory cytokine levels in mice with polymicrobial sepsis.
Department of Surgery, Shiga University of Medical Science, Japan.
Yoshitaka
Y
Uji
Hiroshi
H
Yamamoto
Hiroshi
H
Tsuchihashi
Kazuhisa
K
Maeda
Tohru
T
Funahashi
Iichirou
I
Shimomura
Tomoharu
T
Shimizu
Yoshihiro
Y
Endo
Tohru
T
Tani
D052242:Adiponectin / Q000097:blood / Q000172:deficiency*; D000818:Animals; D002432:Cecum / Q000601:surgery; D004731:Endotoxins / Q000097:blood*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000187:drug effects / Q000502:physiology; D000077154:Rosiglitazone; D018805:Sepsis / Q000097:blood* / Q000209:etiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D052242:Adiponectin; D004731:Endotoxins; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone