Beyond insulin resistance in NASH:: TNF-α or adiponectin?
Beyond insulin resistance in NASH:: TNF-α or adiponectin?
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DOI：
10.1002/hep.20280
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发表时间：
2004-07-01
期刊：
影响因子：
13.5
通讯作者：
George, J
中科院分区：
文献类型：
--
作者：
Hui, JM;Hodge, A;George, J
脂联素具有抗脂生和抗炎作用，而肿瘤坏死因子α (tnf - α)降低胰岛素敏感性并具有促炎作用。我们研究了(1)低脂联素血症和tnf - α激活在非酒精性脂肪性肝炎（NASH）的特征程度；(2)109例非酒精性脂肪性肝病（NAFLD）患者的血清中这些标志物的水平是否与组织学变化的严重程度相关，其中包括80例NASH患者和29例单纯性脂肪变性患者。通过多变量分析，与年龄、性别和体重指数相匹配的对照组相比，NASH患者的脂联素水平降低，TNF- α和可溶性TNF受体2 （sTNFR2）升高，但瘦素水平没有升高；这些差异与NASH中胰岛素抵抗的增加无关（通过稳态模型[HOMA-IR]）。与单纯性脂肪变性相比，NASH与较低的脂联素水平和较高的HOMA-IR相关，但tnf - α和sTNFR2水平无显著差异。大多数脂肪性肝炎患者（77%）的脂联素水平低于10马克杯/毫升，HOMA-IR高于3个单位，但只有33%的纯脂肪变性患者有这些发现。HOMA-IR和低血清脂联素也与肝坏死炎症等级增加独立相关。总之，低脂联素血症是NASH的一个独立于胰岛素抵抗的特征。脂联素水平降低与更广泛的坏死性炎症有关，并可能促进NAFLD坏死性炎症形式的发展。
Adiponectin has antilipogenic and anti-inflammatory effects, while tumor necrosis factor alpha (TNF-alpha) reduces insulin sensitivity and has proinflammatory effects. We examined (1) the extent to which hypoadiponectinemia and TNF-alpha activation are features of nonalcoholic steatohepatitis (NASH) and (2) whether serum levels of these markers correlate with the severity of histological changes in 109 subjects with nonalcoholic fatty liver disease (NAFLD), including 80 with NASH and 29 with simple steatosis. By multivariate analysis, subjects with NASH had reduced adiponectin level and increased TNF-alpha and soluble TNF receptor 2 (sTNFR2) - but not leptin levels, compared with controls matched by age, sex, and body mass index; these differences were independent of the increased insulin resistance (by homeostasis model [HOMA-IR]) in NASH. When compared with simple steatosis, NASH was associated with lower adiponectin levels and higher HOMA-IR, but there were no significant differences in the levels of TNF-alpha and sTNFR2. The majority of subjects with steatohepatitis (77%) had adiponectin levels less than 10 mug/mL and HOMA-IR greater than 3 units, but only 33% of those with pure steatosis had these findings. HOMA-IR and low serum adiponectin were also independently associated with increased grades of hepatic necroinflammation. In conclusion, hypoadiponectinemia is a feature of NASH independent of insulin resistance. Reduced adiponectin level is associated with more extensive necroinflammation and may contribute to the development of necroinflammatory forms of NAFLD.