Adiponectin protects LPS-induced liver injury through modulation of TNF-α in KK-Ay obese mice
Adiponectin protects LPS-induced liver injury through modulation of TNF-α in KK-Ay obese mice
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DOI：
10.1002/hep.20282
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发表时间：
2004-07-01
期刊：
影响因子：
13.5
通讯作者：
Yoshimatsu, H
中科院分区：
文献类型：
--
作者：
Masaki, T;Chiba, S;Yoshimatsu, H
脂联素是一种存在于脂肪组织中的脂肪细胞因子，其受体广泛分布于包括肝脏在内的多种组织中。本研究旨在探讨脂联素在脂多糖（LPS）诱导的KK-Ay肥胖小鼠肝损伤中的作用。我们分析了脂联素预处理对D-氨基半乳糖/脂多糖（GalN/LPS）诱导的KK-Ay肥胖小鼠肝损伤的影响。GalN/LPS处理诱导血液中天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平的显著增加、肝细胞的凋亡和坏死变化，和/或显示出高度的致死性。GalN/LPS诱导的肝损伤在KK-Ay肥胖小鼠中比在瘦对照中更明显。脂联素预处理可改善GalN/LPS诱导的血清AST和ALT水平升高以及肝细胞凋亡和坏死变化，从而降低致死率。此外，脂联素预处理减弱了GalN/LPS诱导的血清和肝脏肿瘤坏死因子α（TNF-α）水平升高以及肝脏过氧化物酶体增殖物激活受体（PPAR）α信使RNA表达增加。此外，与对照组相比，体外用脂联素预处理的KK-Ay肥胖小鼠的腹腔巨噬细胞表现出LPS诱导的TNF-α产生减少。最后，脂联素预处理也改善了TNF-α诱导的肝损伤。总之，这些发现表明脂联素通过抑制KK-Ay肥胖小鼠TNF-α的合成和/或释放来预防LPS诱导的肝损伤。
Adiponectin, an adipocytokine, has been identified in adipose tissue, and its receptors are widely distributed in many tissues, including the liver. The present study was performed to clarify the role of adiponectin in lipopolysaccharide (LPS)-induced liver injury using KK-Ay obese mice. We analyzed the effects of adiponectin pretreatment on liver injury induced by D-galactosamine/LPS (GalN/LPS) in KK-Ay obese mice. GalN/LPS treatment induced significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the blood, apoptotic and necrotic changes in hepatocytes, and/or showed a high degree of lethality. The GalN/LPS-induced liver injury was more pronounced in KK-Ay obese mice than in lean controls. Pretreatment with adiponectin ameliorated the GalN/LPS-induced elevation of serum AST and ALT levels and the apoptotic and necrotic changes in hepatocytes, resulting in a reduction in lethality. In addition, pretreatment with adiponectin attenuated the GalN/LPS-induced increases in serum and hepatic tumor necrosis factor alpha (TNF-alpha) levels and increased peroxisome proliferator-activated receptor (PPAR) alpha messenger RNA expression in the liver. Furthermore, abdominal macrophages from KK-Ay obese mice pretreated with adiponectin in vitro exhibited decreased LPS-induced TNF-alpha production compared with controls. Finally, adiponectin pretreatment also ameliorated TNF-alpha-induced liver injury. In conclusion, these findings suggest that adiponectin prevents LPS-induced hepatic injury by inhibiting the synthesis and/or release of TNF-alpha of KK-Ay obese mice.