Elevated fasting ethanol levels in peripheral blood frequently found in metabolic dysfunction-associated steatohepatitis (MASLD) patients even in the absence of alcohol consumption are discussed to contribute to disease development. To test the hypothesis that besides an enhanced gastrointestinal synthesis a diminished alcohol elimination through alcohol dehydrogenase (ADH) may also be critical herein, we determined fasting ethanol levels and ADH activity in livers and blood of MASLD patients and in wild-type ± anti-TNFα antibody (infliximab) treated and TNFα mice fed a MASLD-inducing diet. Blood ethanol levels were significantly higher in patients and wild-type mice with MASLD while relative ADH activity in blood and liver tissue was significantly lower compared to controls. Both alterations were significantly attenuated in MASLD diet-fed TNFα mice and wild-type mice treated with infliximab. Moreover, alcohol elimination was significantly impaired in mice with MASLD. In models, TNFα but not IL-1β or IL-6 significantly decreased ADH activity. Our data suggest that elevated ethanol levels in MASLD patients are related to TNFα-dependent impairments of ADH activity.

中文翻译：

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MASLD 与乙醇脱氢酶 (ADH) 活性受损和血液乙醇水平升高有关：TNFα 和 JNK 的作用

代谢功能障碍相关脂肪性肝炎 (MASLD) 患者即使在没有饮酒的情况下也经常发现外周血中空腹乙醇水平升高，这被认为有助于疾病的发展。为了检验这一假设，即除了增强胃肠道合成外，通过乙醇脱氢酶 (ADH) 减少酒精消除也可能在这里至关重要，我们测定了 MASLD 患者和野生型 ± 抗 TNFα 患者肝脏和血液中的空腹乙醇水平和 ADH 活性抗体（英夫利昔单抗）治疗和 TNFα 小鼠喂食诱导 MASLD 的饮食。与对照组相比，患有 MASLD 的患者和野生型小鼠的血液乙醇水平显着较高，而血液和肝组织中的相对 ADH 活性显着较低。在 MASLD 饮食喂养的 TNFα 小鼠和接受英夫利昔单抗治疗的野生型小鼠中，这两种改变均显着减弱。此外，患有 MASLD 的小鼠的酒精消除能力显着受损。在模型中，TNFα（而非 IL-1β 或 IL-6）显着降低了 ADH 活性。我们的数据表明，MASLD 患者乙醇水平升高与 TNFα 依赖性 ADH 活性受损有关。