Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation
Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation
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DOI：
10.1016/j.yexmp.2011.08.001
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发表时间：
2011-12-01
影响因子：
3.6
通讯作者：
Hellerbrand, Claus
中科院分区：
文献类型：
--
作者：
Kirovski, Georgi;Dorn, Christoph;Hellerbrand, Claus
非酒精性脂肪性肝病（NAFLD）与肥胖和代谢综合征密切相关。它包括从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH）的临床病理学范围。后者在促炎细胞浸润后发展，被广泛认为是NAFLD进展中的第一个相关病理生理步骤。趋化因子单核细胞趋化蛋白1（MCP-1）在肝脏炎症和纤维化的进展中起重要作用，并且在NASH中已经描述了增加的肝脏表达和循环血清水平。在这里，我们的目的是研究MCP-1在单纯性肝脂肪变性中的表达。在喂食高脂肪饮食的小鼠在没有显著肝脏炎症的情况下发生肝脏脂肪变性，但与喂食标准食物的对照小鼠相比，肝脏MCP-1表达升高。有趣的是，高脂饮食喂养的小鼠具有显著更高的MCP-1血清水平，并且MCP-1 mRNA表达在内脏脂肪组织中显著增加。此外，MCP-1血清水平也在超声诊断的NAFLD患者中升高，并与体重指数和空腹血糖相关。总之，我们的数据表明，肝脏和脂肪组织作为细胞来源的循环MCP-1水平升高已经在早期阶段的肝脂肪变性。由于来源于内脏脂肪组织的MCP-1以高浓度通过门静脉循环到达肝脏，因此其可能显著促进单纯性脂肪变性向NASH的进展。(C)2011 Elsevier Inc. All rights reserved.
Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and the metabolic syndrome. It encompasses a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). The latter develops upon pro-inflammatory cell infiltration and is widely considered as the first relevant pathophysiological step in NAFLD-progression. The chemokine monocyte chemoattractant protein 1 (MCP-1) plays an important role in the progression of hepatic inflammation and fibrosis, and both increased hepatic expression and circulating serum levels have been described in NASH. Here, we aimed to investigate MCP-1 expression in simple hepatic steatosis. Upon feeding a high-fat diet mice developed hepatic steatosis in the absence of significant hepatic inflammation, but elevated hepatic MCP-1 expression compared to control mice fed a standard chow. Interestingly, high-fat diet fed mice had significantly higher MCP-1 serum levels, and MCP-1 mRNA expression was significantly increased in visceral adipose tissue. Furthermore, MCP-1 serum levels were also elevated in patients with ultrasound-diagnosed NAFLD and correlated with the body-mass index and fasting glucose. In conclusion, our data indicate both the liver and adipose tissue as cellular sources of elevated circulating MCP-1 levels already in the early phase of hepatic steatosis. Since MCP-1 derived from visceral adipose tissue reaches the liver via portal circulation at high concentrations it may significantly contribute to the progression of simple steatosis to NASH. (C) 2011 Elsevier Inc. All rights reserved.