The ameliorating effect of rosiglitazone on experimental nonalcoholic steatohepatitis is associated with regulating adiponectin receptor expression in rats.
Although nonalcoholic steatohepatitis (NASH) is associated with insulin resistance partly due to reduced levels of circulating adiponectin, the role of adiponectin receptors including adiponectin receptor 1 and adiponectin receptor 2 in adipose tissues in NASH remains controversial. The present study showed that there was a marked decline in adiponectin receptor 1 and adiponectin receptor 2 expressions in liver and visceral fat, and these expressions were elevated in muscle of NASH rats 12weeks after oral administration of a high-fat diet. An 8-week continuous treatment with rosiglitazone, a peroxisome proliferator-activated receptors γ (PPAR γ) agonist improved the histological lesions markedly in liver of NASH rats, and concurrently increased mRNA and protein expressions of adiponectin receptor 1 and adiponectin receptor 2 in liver and visceral fat, with down-regulation of the two receptors in muscle. There was a negative correlation between the ratio of adiponectin receptors/β-actin protein and serum TNF-α in the liver and visceral fat, and a positive correlation in muscle. Additionally, rosiglitazone increased circulating adiponectin, which was negatively correlated with serum TNF-α. These results indicated that rosiglitazone improved NASH by directly modulating adiponectin receptor 1 and adiponectin receptor 2 in various adipose tissues, or indirectly possibly via decreasing serum TNF-α.
Department of Gastroenterology, Zhabei District Central Hospital, Shanghai 200070, China. liusu2222@163.com
Su
S
Liu
Han-Jun
HJ
Wu
Zong-Qi
ZQ
Zhang
Qing
Q
Chen
Bin
B
Liu
Jian-Ping
JP
Wu
Liang
L
Zhu
D052242:Adiponectin / Q000097:blood / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D052242:Adiponectin; D004041:Dietary Fats; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D000077154:Rosiglitazone