Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Redox Biol. 2023 Oct;66:102870. doi: 10.1016/j.redox.2023.102870. Epub 2023 Sep 1.
Tumor necrosis factor alpha (TNFα) is thought to be a critical factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we determined the effects of a treatment with the anti-TNFα antibody infliximab and a genetic deletion of TNFα, respectively, in the development of non-obese diet-induced early metabolic dysfunction-associated steatohepatitis (MASH) in mice. The treatment with infliximab improved markers of liver damage in mice with pre-existing early MASH. In TNFα mice, the development of early signs of MASH and insulin resistance was significantly attenuated compared to wild-type animals. While mRNA expression of proinflammatory cytokines like interleukin 1β (Il1b) and interleukin 6 (Il6) were significantly lower in livers of MASH-diet-fed TNFα mice compared to wild-type mice with early MASH, markers of intestinal barrier function were similarly impaired in both MASH-diet-fed groups compared to controls. Our data suggest that TNFα is a key regulator of hepatic inflammation and insulin resistance associated with the development of early non-obese MASH.
肿瘤坏死因子-α（TNFα）被认为是代谢功能障碍相关脂肪性肝病（MASLD）发展的关键因素。在这里，我们分别确定了抗 TNFα 抗体英夫利昔单抗治疗和 TNFα 基因缺失对非肥胖饮食诱导的早期代谢功能障碍相关脂肪性肝炎（MASH）在小鼠中的发展的影响。英夫利昔单抗治疗改善了患有早期 MASH 的小鼠的肝损伤标志物。与野生型动物相比，TNFα 小鼠的早期 MASH 体征和胰岛素抵抗的发展明显减弱。尽管 MASH 饮食喂养的 TNFα 小鼠肝脏中促炎细胞因子（如白细胞介素 1β（Il1b）和白细胞介素 6（Il6））的 mRNA 表达明显低于早期 MASH 的野生型小鼠，但两组 MASH 饮食喂养的小鼠的肠道屏障功能标志物与对照组相比均有类似的损害。我们的数据表明，TNFα 是与早期非肥胖性 MASH 发展相关的肝炎症和胰岛素抵抗的关键调节剂。
