Changes in phosphatidylcholine levels in the liver have been associated with the development of metabolic dysfunction–associated steatotic liver disease. Here, the effects of supplementing phosphatidylcholine on the development of early signs of metabolic dysfunction–associated steatohepatitis were assessed. Male and female C57BL/6J mice were fed a liquid control or a fructose-, fat-, and/or cholesterol-rich diet for 7 or 8 weeks. The diets of female mice were fortified ± phosphatidylcholine (12.5 mg/g diet). In liver tissue and portal blood, indices of liver damage, inflammation, and bacterial endotoxemia were measured. J774A.1 cells and human monocytes preincubated with phosphatidylcholine (0.38 mmol/L) were challenged with lipopolysaccharide (50–100 ng/mL) ± the peroxisome proliferator-activated receptor γ (PPARγ) activator pioglitazone (10 μmol/L) or ± a liver receptor homolog 1 (LRH-1) antagonist 1-(3′-[1-(2-[4-morpholinyl]ethyl)-1H-pyrazol-3-yl]-3-biphenylyl)ethanon (1–10 μmol/L). In fructose-, fat-, and/or cholesterol-rich diet–fed mice the development of fatty liver and the beginning of inflammation were associated with significantly lower hepatic phosphatidylcholine levels when compared with controls. Supplementing phosphatidylcholine significantly attenuated the development of fatty liver and inflammation, being associated with protection against the induction of PPARγ2, and activation of nuclear factor of κ light polypeptide gene enhancer in B-cell inhibitor α whereas expression was unchanged. The protective effects of phosphatidylcholine on the lipopolysaccharide-induced activation of J774A.1 cells and human monocytes were attenuated significantly by the PPARγ activator pioglitazone and the LRH-1 antagonist. Our data suggest that phosphatidylcholine levels in the liver are lower in early metabolic dysfunction–associated steatohepatitis in mice and that supplementation of phosphatidylcholine can diminish the development of metabolic dysfunction–associated steatotic liver disease through mechanisms involving LRH-1/PPARγ2/ nuclear factor κ-light-chain enhancer of activated B-cell signaling.

中文翻译：

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口服补充磷脂酰胆碱可减轻雌性 C57BL/6J 小鼠饮食引起的代谢功能障碍相关脂肪性肝炎的发作

肝脏中磷脂酰胆碱水平的变化与代谢功能障碍相关的脂肪肝病的发生有关。在此，评估了补充磷脂酰胆碱对代谢功能障碍相关脂肪性肝炎早期症状发展的影响。雄性和雌性 C57BL/6J 小鼠喂食液体对照或富含果糖、脂肪和/或胆固醇的饮食 7 或 8 周。雌性小鼠的饮食中强化了磷脂酰胆碱（12.5 mg/g 饮食）。在肝组织和门静脉血中，测量肝损伤、炎症和细菌内毒素血症的指数。用脂多糖 (50–100 ng/mL) ± 过氧化物酶体增殖物激活受体 γ (PPARγ) 激活剂吡格列酮 (10 μmol/L) 或 ± a 攻击用磷脂酰胆碱 (0.38 mmol/L) 预孵育的 J774A.1 细胞和人单核细胞肝受体同源物 1 (LRH-1) 拮抗剂 1-(3′-[1-(2-[4-吗啉基]乙基)-1H-吡唑-3-基]-3-联苯基)乙酮 (1–10 μmol/ L）。与对照组相比，在富含果糖、脂肪和/或胆固醇的饮食喂养的小鼠中，脂肪肝的发生和炎症的开始与肝磷脂酰胆碱水平显着降低有关。补充磷脂酰胆碱可显着减轻脂肪肝和炎症的发展，这与防止 PPARγ2 的诱导以及 B 细胞抑制剂 α 中 κ 轻链多肽基因增强子核因子的激活有关，而表达却没有变化。 PPARγ 激活剂吡格列酮和 LRH-1 拮抗剂显着减弱了磷脂酰胆碱对脂多糖诱导的 J774A.1 细胞和人单核细胞激活的保护作用。我们的数据表明，小鼠早期代谢功能障碍相关的脂肪性肝炎中肝脏中的磷脂酰胆碱水平较低，补充磷脂酰胆碱可以通过涉及 LRH-1/PPARγ2/核因子 κ- 的机制减少代谢功能障碍相关的脂肪肝病的发展。激活 B 细胞信号传导的轻链增强剂。