Bioorthogonal Stimulated Raman Scattering Imaging Uncovers Lipid Metabolic Dynamics in Drosophila Brain During Aging.
Bioorthogonal Stimulated Raman Scattering Imaging Uncovers Lipid Metabolic Dynamics in Drosophila Brain During Aging.
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生物正交受激拉曼散射成像揭示果蝇衰老过程中脑脂代谢的动态变化
DOI：
10.1089/genbio.2023.0017
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发表时间：
2023-06
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通讯作者：
Yajuan Li;Phyllis Chang;Shriya Sankaran;Hongje Jang;Yuhang Nie;Audrey Zeng;Sahran Hussain;Jane Y. Wu;Xu-Qiao Chen;Lingyan Shi
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作者：
Yajuan Li;Phyllis Chang;Shriya Sankaran;Hongje Jang;Yuhang Nie;Audrey Zeng;Sahran Hussain;Jane Y. Wu;Xu-Qiao Chen;Lingyan Shi
研究表明，脑脂质代谢与生物衰老有关，并受饮食和基因操纵的影响；然而，潜在的机制是难以捉摸的。高分辨率成像技术提出了一种新颖而有效的方法来了解原位脂质代谢动力学。利用受刺激拉曼散射显微镜（DO-SRS）探测氘水（D2O），我们发现果蝇大脑中的脂质代谢活性随着年龄的增长而下降，并以性别依赖的方式下降。雌蝇脂质周转减少的发生时间早于雄蝇。饮食限制（DR）和下调胰岛素/IGF-1信号通路（IIS）是老年果蝇延长寿命的两种途径，可显著提高脑脂质代谢。将SRS成像与氘化生物正交探针（氘化葡萄糖和氘化醋酸盐）相结合，我们发现，在DR处理和IIS通路下调的情况下，脑代谢转向使用醋酸盐作为脂质合成的主要碳源。本研究首次在单细胞器（脂滴）水平上直接可视化和量化果蝇脑脂质周转的时空变化。我们的研究不仅展示了一种原位研究脑脂质代谢活动的新方法，而且阐明了衰老、饮食和遗传操纵对脑脂质代谢调节的相互作用。
Studies have shown that brain lipid metabolism is associated with biological aging and influenced by dietary and genetic manipulations; however, the underlying mechanisms are elusive. High-resolution imaging techniques propose a novel and potent approach to understanding lipid metabolic dynamics in situ. Applying deuterium water (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy, we revealed that lipid metabolic activity in Drosophila brain decreased with aging in a sex-dependent manner. Female flies showed an earlier occurrence of lipid turnover decrease than males. Dietary restriction (DR) and downregulation of insulin/IGF-1 signaling (IIS) pathway, two scenarios for lifespan extension, led to significant enhancements of brain lipid turnover in old flies. Combining SRS imaging with deuterated bioorthogonal probes (deuterated glucose and deuterated acetate), we discovered that, under DR treatment and downregulation of IIS pathway, brain metabolism shifted to use acetate as a major carbon source for lipid synthesis. For the first time, our study directly visualizes and quantifies spatiotemporal alterations of lipid turnover in Drosophila brain at the single organelle (lipid droplet) level. Our study not only demonstrates a new approach for studying brain lipid metabolic activity in situ but also illuminates the interconnection of aging, dietary, and genetic manipulations on brain lipid metabolic regulation.