Visualizing deuterated lipids via stimulated Raman scattering microscopy

Cellular lipid metabolism is a highly diverse and adaptive process, significantly influenced by exogenous metabolites, which is also a key link in the pathogenic mechanism of various metabolic diseases. Compared to traditional biochemical assays or genomic/proteomic methods, optical imaging technology can achieve real-time tracking of metabolic processes and provide sub-micrometer spatial resolution, promising new insights for understanding metabolic regulatory mechanisms at the subcellular level. This study combines a deuterated fatty acid labeling strategy with stimulated Raman scattering (SRS) microscopy to visually track the distribution of deuterated lipids within subcellular structures and to investigate the influence of different types of fatty acids on their dynamic regulation. The results show that the uptaken deuterated fatty acids are mainly enriched in organelles such as the endoplasmic reticulum and lipid droplets, and their distribution is closely related to the uptake amount and duration. The supply of different types of fatty acids further alters the distribution pattern of deuterated lipids within the cell and affects cellular function. This study reveals a dynamic allocation mechanism for fatty acids and lipids within the cell, which is of great significance for the in-depth understanding of dietary intervention, lipid homeostasis imbalance, and the onset and development of related metabolic diseases.