Lipophagy as a form of autophagy, can degrade lipid droplets, thereby acting as a critical regulator of cellular lipid metabolism, helping maintain the intracellular lipid homeostasis. In this study, we developed LP-SCUN, a far-red fluorescent probe for pinpointing lipid droplets with high sensitivity to solvent polarity. This probe allows for in situ imaging of lipophagy, tracking how lipid droplets move from non-polar to polar environments within lysosomes, leading to noticeable changes in fluorescence signals. The triphenylamine and triethylene glycol monomethyl ether groups of LP-SCUN facilitated its selective binding toward lipid droplets. Significantly, lipophagy and subsequent formation of autolysosomes decreased the environmental polarity, leading to a significant decrease in red fluorescence intensity (λ_ex = 500 nm and λ_em = 643 nm). As such LP-SCUN was suitable for the in situ and real-time tracking of the cellular lipophagic processes. With this research we used LP-SCUN to elucidate the mechanism of lipid metabolism in liver cells of palmitate-induced hyperlipidemia cell models and high-fat diet-induced hyperlipidemia animal models. The results indicated that non-alcoholic fatty liver disease (NAFLD) can trigger an increase in cell lipophagy levels, while the inhibition of cell lipophagy can effectively alleviate the damage caused by NAFLD to cells and liver tissue in mice.

中文翻译：

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利用具有大斯托克斯位移的远红外荧光探针揭示 NAFLD 触发的脂肪吞噬过程中脂滴极性的动态变化


脂肪吞噬作为自噬的一种形式，可以降解脂滴，从而作为细胞脂质代谢的关键调节因子，有助于维持细胞内脂质稳态。在这项研究中，我们开发了 LP-SCUN，这是一种远红外荧光探针，用于精确定位对溶剂极性高度敏感的脂滴。该探针允许对脂肪吞噬进行原位成像，跟踪脂滴如何在溶酶体内从非极性环境移动到极性环境，从而导致荧光信号的显着变化。LP-SCUN 的三苯胺和三甘醇单甲醚基团促进了其对脂滴的选择性结合。显著显著的，脂肪吞噬和随后的自噬溶酶体形成降低了环境极性，导致红色荧光强度显著降低（λ_ex = 500 nm 和 λ_em = 643 nm）。因此，LP-SCUN 适用于细胞吞脂过程的原位和实时跟踪。通过这项研究，我们使用 LP-SCUN 阐明了棕榈酸酯诱导的高脂血症细胞模型和高脂饮食诱导的高脂血症动物模型的肝细胞脂质代谢机制。结果表明，非酒精性脂肪性肝病 （NAFLD） 可触发细胞脂肪吞噬水平升高，而抑制细胞脂肪吞噬可有效减轻 NAFLD 对小鼠细胞和肝组织造成的损伤。