Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease.
OBJECTIVE
To investigate the effects of rosiglitazone (RGZ) on expression of interleukin-18 (IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease (NAFLD) rats.


METHODS
Twenty-eight Sprague-Dawley (SD) rats were randomly divided into control, NAFLD, and RGZ treated NAFLD groups. A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk. The NAFLD animals were treated with RGZ or vehicle for the last 4 wk (week 9-12) and then sacrificed to obtain liver tissues. Histological changes were analyzed with HE, oil red O and Masson's trichrome staining. Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis.


RESULTS
The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group. Steatosis, inflammation and fibrosis, found in the liver of NAFLD rats, were significantly improved 4 wk after RGZ treatment. The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.


CONCLUSIONS
RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats. The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.
Wang
Hai-Ning
HN
Department of Endocrinology, Peking University, Third Hospital, Beijing 100191, China.
Wang
Yan-Rong
YR
Liu
Guo-Qiang
GQ
Liu
Zhe
Z
Wu
Pei-Xian
PX
Wei
Xiao-Ling
XL
Hong
Tian-Pei
TP
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D020382:Interleukin-18 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D020382:Interleukin-18; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D020170:Caspase 1