Department of Gastroenterology, Zhabei District Central Hospital, Shanghai 200070, China.
Eur J Pharmacol. 2011 Jan 10;650(1):384-9. doi: 10.1016/j.ejphar.2010.09.082. Epub 2010 Oct 20.
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.
虽然非酒精性脂肪性肝炎（NASH）与胰岛素抵抗有关，部分原因是循环脂联素水平降低，但脂肪组织中脂联素受体（包括脂联素受体 1 和脂联素受体 2）在 NASH 中的作用仍存在争议。本研究显示，高脂肪饮食喂养 12 周后，NASH 大鼠肝脏和内脏脂肪中的脂联素受体 1 和脂联素受体 2 表达明显下降，而肌肉中的表达升高。连续 8 周给予过氧化物酶体增殖物激活受体 γ（PPARγ）激动剂罗格列酮治疗可显著改善 NASH 大鼠的肝组织学病变，同时增加肝和内脏脂肪中脂联素受体 1 和脂联素受体 2 的 mRNA 和蛋白表达，而肌肉中的两种受体表达下调。肝脏和内脏脂肪中脂联素受体/β-肌动蛋白蛋白与血清 TNF-α的比值呈负相关，而肌肉中呈正相关。此外，罗格列酮增加了循环脂联素，其与血清 TNF-α呈负相关。这些结果表明，罗格列酮通过直接调节各种脂肪组织中的脂联素受体 1 和脂联素受体 2，或通过间接降低血清 TNF-α，改善了 NASH。
