Obstructive sleep apnea and non-alcoholic Fatty liver disease: is the liver another target?
Obstructive sleep apnea and non-alcoholic Fatty liver disease: is the liver another target?
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DOI：
10.3389/fneur.2012.00149
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发表时间：
2012
影响因子：
3.4
通讯作者：
Polotsky VY
中科院分区：
文献类型：
--
作者：
Mirrakhimov AE;Polotsky VY
阻塞性睡眠呼吸暂停（OSA）是睡眠期间上呼吸道的反复阻塞，导致间歇性缺氧（IH）。OSA与代谢综合征的所有组成部分以及非酒精性脂肪性肝病（NAFLD）相关。NAFLD是一种常见的疾病，其严重程度从单纯性肝脂肪变性到脂肪性肝炎（NASH）、肝纤维化和肝硬化。NAFLD诊断和分期的金标准是肝活检。肥胖和胰岛素抵抗导致肝脏脂肪变性，但进展为NASH的原因尚不清楚。新出现的证据表明，OSA可能在肝脂肪变性的进展和NASH的发展中发挥作用。几项横断面研究表明，OSA患者IH的严重程度可预测肝活检中NAFLD的严重程度。然而，既没有前瞻性研究，也没有持续气道正压通气治疗的干预性研究。在小鼠模型中的研究表明，IH导致肝脏中的甘油三酯积累和肝脏损伤以及肝脏炎症。小鼠模型提供了对肝损伤发病机制的认识，表明（1）IH通过诱导脂肪组织脂解和增加游离脂肪酸（FFA）流入肝脏加速肝脂肪变性的进展;（2）IH上调肝脏中的脂质生物合成途径;（3）IH诱导肝脏中的氧化应激;（4）IH诱导肝脏中的氧化应激;（5）IH诱导肝脏中的氧化应激。（4）IH上调缺氧诱导因子1 α和可能的HIF-2 α，这可能增加肝脂肪变性并诱导肝脏炎症和纤维化。然而，FFA和不同的转录因子在IH诱导的NAFLD发病机制中的作用尚未确定。因此，多条证据表明OSA的IH可能有助于NAFLD的进展，但尚未在小鼠模型中进行明确的临床研究和实验。
Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH). OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD). NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH), liver fibrosis, and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA) flux into the liver; (2) IH up-regulates lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.