Hepatic steatosis, also known as fatty liver disease, occurs due to abnormal lipid accumulation in the liver. It has been known that gut absorption also plays an important role in the mechanism underlying hepatic steatosis. Conventional in vitro cell culture models have limitations in recapitulating the mechanisms of hepatic steatosis because it does not include the gut absorption process. Previously, we reported development of a microfluidic gut–liver chip that can recapitulate the gut absorption of fatty acids and subsequent lipid accumulation in liver cells. In this study, we performed a series of experiments to verify that our gut–liver chip reproduces various aspects of hepatic steatosis. The absorption of fatty acids was evaluated under various culture conditions. The anti-steatotic effect of turofexorate isopropyl (XL-335) and metformin was tested, and both drugs showed different action mechanisms. In addition, the oxidative stress induced by lipid absorption was evaluated. Our results demonstrate the potential of the gut–liver chip for use as a novel, physiologically realistic in vitro model to study fatty liver disease.

中文翻译：

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基于肠-肝芯片的体外肝脂肪变性模型

肝脏脂肪变性，也称为脂肪肝疾病，是由于肝脏中异常的脂质积累而发生的。众所周知，肠道吸收在肝脏脂肪变性的机制中也起着重要作用。传统的体外细胞培养模型在概括肝脂肪变性的机制方面存在局限性，因为它不包括肠道吸收过程。此前，我们报道了一种微流控肠肝芯片的开发，该芯片可以概括脂肪酸的肠道吸收和随后肝细胞中的脂质积累。在这项研究中，我们进行了一系列实验来验证我们的肠肝芯片再现了肝脏脂肪变性的各个方面。在各种培养条件下评估脂肪酸的吸收。测试了turofexorate isopropyl（XL-335）和二甲双胍的抗脂肪变性作用，两种药物表现出不同的作用机制。此外，还评估了由脂质吸收引起的氧化应激。我们的研究结果证明了肠肝芯片作为一种新颖的、生理上现实的体外模型来研究脂肪肝疾病的潜力。