The study of lipid distribution and function within living organisms is crucial for understanding aging, disease, and metabolism. Caenorhabditis elegans, a transparent roundworm, serves as an ideal model for investigating fat storage due to its genetic similarities to humans and well-defined anatomy. However, visualizing lipids at a high resolution in such a small organism has presented significant technical challenges.
A research team at Okayama University in Japan, led by Professor Masazumi Fujiwara and Ph.D. student Sara Mandic, collaborated with Professor Ron M. A. Heeren of Maastricht University in the Netherlands to develop a novel microfluidics-based workflow. This innovative approach enables high-resolution, 3D imaging of lipids in C. elegans. Their groundbreaking findings were published in the prestigious journal Scientific Reports on July 8, 2025.
The team combined matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with traditional lipid staining techniques to map both the identity and location of lipid molecules within the worm. By immobilizing young adult nematodes on a custom microfluidic chip, embedding them in a gelatin–carboxymethyl cellulose mixture, sectioning them using a cryotome, and analyzing them through MALDI-MSI, the researchers were able to preserve internal structures and achieve unprecedented clarity in lipid imaging.
Mandic explains, “This method allows us to map lipid distributions in C. elegans with unparalleled spatial resolution while maintaining the integrity of internal structures.” This innovative workflow overcomes the limitations of conventional lipid analysis techniques by simultaneously identifying specific lipid molecules and illustrating their precise locations within the organism’s body.
Using this approach, the researchers identified distinct lipid clusters in various anatomical regions of C. elegans, such as the pharynx, intestine, and reproductive system. For example, they discovered a lipid associated with cholesterol metabolism primarily located in the pharynx and anterior intestine, indicating a potential role in nutrient absorption. These findings, facilitated by the method’s structural preservation, offer valuable insights into how fat molecules are organized and function across different tissues.
Furthermore, the team extended their analysis to create three-dimensional reconstructions of individual nematodes by aligning and stacking consecutive tissue slices. This advanced visualization technique allowed them to observe the precise arrangement of lipids throughout the entire organism, providing unprecedented anatomical detail.
The reproducibility and accuracy of this method demonstrate its potential to revolutionize lipid biology research. By visualizing lipid dynamics within specific tissues of a single nematode, researchers can investigate how genetic mutations, environmental stressors, drug treatments, and aging impact lipid behavior—a critical step in understanding human health and disease.
As C. elegans shares essential biological pathways with humans, this technique holds immense promise for biomedical research. The team plans to apply this workflow to different C. elegans strains, including those with disease-related mutations, and integrate it with lipid quantification tools to advance our understanding of lipid metabolism and its implications for aging, metabolic disorders, and disease mechanisms.
In conclusion, this study provides researchers with a powerful tool for examining fat metabolism at an organ-specific level in C. elegans, offering new insights into complex biological processes and paving the way for future discoveries in the field of lipid biology.
