Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice.
OBJECTIVE
To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide (LPS) -induced liver injury.


METHODS
D-galactosamine (GalN) and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with LPS.


RESULTS
In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-alpha (TNF-alpha) and significantly reduced IL-10 levels compared with wild type mice. TNF-alpha gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-alpha levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without adiponectin-pre-treatment.


CONCLUSIONS
Adiponectin supresses TNF-alpha production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.
Matsumoto
Hitoshi
H
Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Japan.
Tamura
Shinji
S
Kamada
Yoshihiro
Y
Kiso
Shinichi
S
Fukushima
Juichi
J
Wada
Akira
A
Maeda
Norikazu
N
Kihara
Shinji
S
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
Shimomura
Iichiro
I
Hayashi
Norio
N
D052242:Adiponectin / Q000235:genetics* / Q000502:physiology; D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D005688:Galactosamine / Q000009:adverse effects* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D007728:Kupffer Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D052242:Adiponectin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D016753:Interleukin-10; D005688:Galactosamine; D007371:Interferon-gamma; D000410:Alanine Transaminase