In the past 30 years, incidences of non-alcoholic fatty liver disease (NAFLD) has risen by 30%. However, there is still no clear mechanism or accurate method of anticipating liver failure. Here we reveal the phase transitions of liquid crystalline qualities in hepatic lipid droplets (HLDs) as a novel method of anticipating prognosis. NAFLD was induced by feeding C57BL/6J mice on a high-fat (HiF) diet. These NAFLD livers were then evaluated under polarized microscopy, X-ray diffraction and small-angle scattering, lipid component chromatography analysis and protein expression analysis. Optically active HLDs from mouse model and patient samples were both then confirmed to have liquid crystal characteristics. Liver MAP1LC3A expression was then evaluated to determine the role of autophagy in liquid crystal HLD (LC-HLD) formation. Unlike the normal diet cohort, HiF diet mice developed NAFLD livers containing HLDs exhibiting Maltese cross birefringence, phase transition, and fluidity signature to liquid crystals. These LC-HLDs transitioned to anisotropic crystal at 0 °C and remain crystalline. Temperature increase to 42 °C causes both liquid crystal and crystal HLDs to convert to isotropic droplet form. These isotropic HLDs successfully transition to anisotropic LC with fast temperature decrease and anisotropic crystal with slow temperature decrease. These findings were duplicated in patient liver. Patient LC-HLDs with no inner optical activity were discovered, hinting at lipid saturation as the mechanism through which HLD acquire LC characteristics. Downregulation of MAP1LC3A in conjunction with increased LC-HLD also implicated autophagy in NAFLD LC-HLD formation. Increasing concentrations of amphiphilic lipids in HLDs favors organization into alternating hydrophilic and hydrophobic layers, which present as LC-HLDs. Thus, evaluating the extent of liquid crystallization with phase transition in HLDs of NAFLD patients may reveal disease severity and predict impending liver damage.

中文翻译：

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非酒精性脂肪性肝病经历与脂肪吞噬增加相关的肝液晶积累

在过去 30 年中，非酒精性脂肪性肝病 (NAFLD) 的发病率上升了 30%。然而，仍然没有明确的机制或准确的方法来预测肝功能衰竭。在这里，我们揭示了肝脂滴 (HLD) 中液晶质量的相变，这是一种预测预后的新方法。NAFLD 是通过以高脂肪 (HiF) 饮食喂养 C57BL/6J 小鼠来诱导的。然后在偏光显微镜、X 射线衍射和小角散射、脂质成分色谱分析和蛋白质表达分析下评估这些 NAFLD 肝脏。然后确认来自小鼠模型和患者样本的光学活性 HLD 都具有液晶特性。然后评估肝脏 MAP1LC3A 表达以确定自噬在液晶 HLD (LC-HLD) 形成中的作用。与正常饮食组不同，HiF 饮食小鼠发育出含有 HLD 的 NAFLD 肝脏，这些 HLD 表现出马耳他交叉双折射、相变和液晶的流动性特征。这些 LC-HLD 在 0°C 时转变为各向异性晶体并保持结晶状态。温度升高到 42 °C 会导致液晶和晶体 HLD 转换为各向同性液滴形式。这些各向同性 HLD 成功地转变为具有快速降温的各向异性 LC 和具有缓慢降温的各向异性晶体。这些发现在患者肝脏中重复。发现了没有内部光学活性的患者 LC-HLD，暗示脂质饱和是 HLD 获得 LC 特性的机制。MAP1LC3A 的下调与增加的 LC-HLD 一起也与 NAFLD LC-HLD 形成中的自噬有关。HLD 中两亲脂质浓度的增加有利于组织成交替的亲水层和疏水层，这些层以 LC-HLD 的形式存在。因此，评估 NAFLD 患者 HLD 中具有相变的液相结晶程度可能揭示疾病严重程度并预测即将发生的肝损伤。