肿瘤坏死因子α (TNFα) 在代谢失调相关脂肪肝疾病 (MASLD) 的发展中被认为是一个关键因素。在本研究中，我们分别确定了抗TNFα抗体英夫利昔单抗 (infliximab) 治疗和TNFα基因缺失对非肥胖饮食所致早期代谢失调相关脂肪肝 (MASH) 在小鼠体内的影响。在具有已存在早期MASH的小鼠中，英夫利昔单抗治疗改善了肝损伤指标。在TNFα基因缺失小鼠中，早期MASH和胰岛素抵抗的发展明显减轻，与野生型动物相比。虽然TNFα基因缺失小鼠MASH饮食组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表达显著低于早期MASH的野生型小鼠，但肠道屏障功能的指标在两组MASH饮食组中相比对照组都受损。我们的数据表明TNFα是与早期非肥胖MASH发展相关的肝脏炎症和胰岛素抵抗的关键调节因子。 版权所有 © 2023 作者。由 Elsevier B.V. 发布，保留所有权利。

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.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.