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.
Uji
Yoshitaka
Y
Department of Surgery, Shiga University of Medical Science, Japan.
Yamamoto
Hiroshi
H
Tsuchihashi
Hiroshi
H
Maeda
Kazuhisa
K
Funahashi
Tohru
T
Shimomura
Iichirou
I
Shimizu
Tomoharu
T
Endo
Yoshihiro
Y
Tani
Tohru
T
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