Elevated endotoxin levels in non-alcoholic fatty liver disease.
Elevated endotoxin levels in non-alcoholic fatty liver disease.
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DOI：
10.1186/1476-9255-7-15
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发表时间：
2010-03-30
期刊：
影响因子：
--
通讯作者：
McTernan PG
中科院分区：
文献类型：
--
作者：
Harte AL;da Silva NF;Creely SJ;McGee KC;Billyard T;Youssef-Elabd EM;Tripathi G;Ashour E;Abdalla MS;Sharada HM;Amin AI;Burt AD;Kumar S;Day CP;McTernan PG
新出现的数据表明，肠道来源的内毒素可能有助于胰岛素抵抗状态下的低度全身性炎症。本研究旨在探讨血清内毒素和炎症标志物在伴有和不伴有2型糖尿病（T2DM）的非酒精性脂肪性肝病（NAFLD）患者中的重要性，并探讨脂肪酶抑制剂奥利司他治疗对其炎症状态的影响。对155例活检证实的NAFLD患者和23例对照者的空腹血清进行内毒素、可溶性CD14 （sCD14）、可溶性肿瘤坏死因子受体II （sTNFRII）和各种代谢参数的分析。NAFLD患者亚组在单独饮食（n = 6）或饮食加奥利司他（n = 8）治疗后6个月和12个月进行重新评估。NAFLD患者的内毒素水平明显高于对照组(NAFLD: 10.6(7.8, 14.8) EU/mL；对照组：3.9(3.2,5.2)EU/mL, p < 0.001)；NAFLD单独产生的内毒素水平与T2DM相当(NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL；非糖尿病患者：10.6(8.5,15.2)EU/mL)，而胰岛素抵抗与血清内毒素有显著相关性（r = 0.27, p = 0.008）。sCD14 （p < 0.01）和sTNFRII （p < 0.001）随纤维化严重程度升高。NAFLD患者的sTNFRII与sCD14呈正相关（r = 0.29, p = 0.004）。在治疗后6个月和12个月，奥利司他治疗NAFLD患者的ALT （p = 0.006）、体重（p = 0.005）和内毒素（p = 0.004）分别显著低于非奥利司他治疗NAFLD的对照组。NAFLD患者的内毒素水平显著升高，与对照组相比，早期纤维化患者的内毒素水平明显升高。这些结果表明，内毒素升高可能是潜在肝损伤的早期指标，可能不需要进行侵入性肝活检。由于内毒素可能促进胰岛素抵抗和炎症，旨在降低NAFLD患者内毒素水平的干预措施可能有助于减轻炎症负担。
Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status. Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or diet plus Orlistat (n = 8). Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM (NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001) increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD subjects (r = 0.29, p = 0.004). Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p = 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively. Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.
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影响因子：
5.3
作者：
Miller, Michelle A.;McTernan, Philip G.;Cappuccio, Francesco P.
通讯作者：
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4.4
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5.8
作者：
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通讯作者：
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