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<p>Disordered lipid metabolism in diabetes is closely associated with structural and functional abnormalities in lipid droplets (LDs). To better investigate these dynamics, we developed a novel fluorescent probe, XY-03, via a comparative screening process for the specific targeting of LDs. XY-03 exhibits high specificity, a large Stokes shift (137&#xa0;nm), excellent photostability, and low cytotoxicity. We successfully applied this probe to track LD accumulation and dynamically monitor changes in microenvironmental viscosity in living cells stimulated with oleic acid (OA), lipopolysaccharide (LPS), or high glucose. Furthermore, XY-03 enabled quantitative detection and differentiation of LD viscosity at the organ level in mouse models, including normal controls, streptozotocin-induced diabetic mice, and metformin-treated mice. Imaging results revealed a significantly higher microenvironmental viscosity of LDs in the livers of diabetic mice compared to normal controls, whereas metformin treatment markedly reduced this viscosity. These findings underscore a strong correlation between elevated LD viscosity and diabetic liver injury. Collectively, our study demonstrates that XY-03 holds considerable potential as a powerful imaging tool for diagnosing and investigating diseases associated with LD viscosity.</p>

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Rational Design of Variable Alkyl Chain-Based Fluorescent Probes for Lipid Droplet Imaging in Diabetic Liver Injury Diagnosis

  • 期刊论文

  • 发表日期：

    2026年7月11日

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  • Tao Qiu,
  • Shijun Chen,
  • Yongwei Limeng,
  • Cailing Fan,
  • Qiye Liu,
  • Chunmei Chen,
  • Wei Shu,
  • Qidi Zhong,
  • Weijie Chi,
  • Chaoyuan Zeng

摘要

Disordered lipid metabolism in diabetes is closely associated with structural and functional abnormalities in lipid droplets (LDs). To better investigate these dynamics, we developed a novel fluorescent probe, XY-03, via a comparative screening process for the specific targeting of LDs. XY-03 exhibits high specificity, a large Stokes shift (137 nm), excellent photostability, and low cytotoxicity. We successfully applied this probe to track LD accumulation and dynamically monitor changes in microenvironmental viscosity in living cells stimulated with oleic acid (OA), lipopolysaccharide (LPS), or high glucose. Furthermore, XY-03 enabled quantitative detection and differentiation of LD viscosity at the organ level in mouse models, including normal controls, streptozotocin-induced diabetic mice, and metformin-treated mice. Imaging results revealed a significantly higher microenvironmental viscosity of LDs in the livers of diabetic mice compared to normal controls, whereas metformin treatment markedly reduced this viscosity. These findings underscore a strong correlation between elevated LD viscosity and diabetic liver injury. Collectively, our study demonstrates that XY-03 holds considerable potential as a powerful imaging tool for diagnosing and investigating diseases associated with LD viscosity.