Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice
Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice
复制标题
脂联素缺乏通过减弱小鼠体内 STAT3 磷酸化来损害肝再生
DOI：
10.1038/labinvest.2009.63
复制
发表时间：
2009-09-01
影响因子：
5
通讯作者：
Wang, Zhu-Gang
中科院分区：
文献类型：
--
作者：
Shu, Run-Zhe;Zhang, Feng;Wang, Zhu-Gang
肝再生是一个非常复杂和精心策划的过程，与涉及细胞因子，生长因子和代谢途径的信号级联相关。脂联素是成熟脂肪细胞分泌的一种脂肪细胞因子，其受体广泛分布于包括肝脏在内的多种组织中。脂联素直接作用于肝脏，在改善肝脏胰岛素敏感性、增加脂肪酸氧化、减轻炎症等方面具有突出作用。为了检验脂联素是肝再生正常进程所必需的这一假设，对野生型和脂联素缺失小鼠进行了2/3部分肝切除术（PH）。与野生型小鼠相比，脂联素基因敲除小鼠表现出肝块再生减少，肝细胞增殖受阻，肝脂质蓄积增加。基因表达分析显示脂联素对脂代谢相关基因的转录有调控作用。此外，抑制肝细胞增殖伴随着信号转导和转录激活蛋白3（STAT 3）活性降低和细胞因子信号转导抑制因子3（Socs 3）转录增强。总之，脂联素缺失小鼠表现出肝再生受损和肝脂肪变性增加。脂联素缺失小鼠中Socs 3表达的增加和随后STAT 3活化的减少可能有助于在PH之后肝再生能力和肝脂质代谢的改变。Laboratory Investigation（2009）89，1043-1052; doi：10.1038/labinvest.2009.63; 2009年6月29日在线发表
Liver regeneration is a very complex and well-orchestrated process associated with signaling cascades involving cytokines, growth factors, and metabolic pathways. Adiponectin is an adipocytokine secreted by mature adipocytes, and its receptors are widely distributed in many tissues, including the liver. Adiponectin has direct actions in the liver with prominent roles to improve hepatic insulin sensitivity, increase fatty acid oxidation, and decrease inflammation. To test the hypothesis that adiponectin is required for normal progress of liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and adiponectin-null mice. Compared to wild-type mice, adiponectin-null mice displayed decreased liver mass regrowth, impeded hepatocyte proliferation, and increased hepatic lipid accumulation. Gene expression analysis revealed that adiponectin regulated the gene transcription related to lipid metabolism. Furthermore, the suppressed hepatocyte proliferation was accompanied with reduced signal transducer and activator of transcription protein 3 (STAT3) activity and enhanced suppressor of cytokine signaling 3 (Socs3) transcription. In conclusion, adiponectin-null mice exhibit impaired liver regeneration and increased hepatic steatosis. Increased expression of Socs3 and subsequently reduced activation of STAT3 in adiponectin-null mice may contribute to the alteration of the liver regeneration capability and hepatic lipid metabolism after PH. Laboratory Investigation (2009) 89, 1043-1052; doi:10.1038/labinvest.2009.63; published online 29 June 2009