In neurodegenerative disease research, lipid droplet metabolism is gaining recognition as a critical modulator of microglial immune function. These triglyceride-rich droplets are essential for regulating microglial activation, cytokine release, and phagocytosis. Their formation and turnover rate have also been identified as key factors for determining pro-inflammatory versus homeostatic microglial responses. In Alzheimer’s disease, intrinsic genetic risk factors such as the APOE4 genotype have been shown to induce undesirable accumulation of lipid droplets in microglia, raising concerns about promoting proper lipid droplet metabolism.
In a 2025 Cell Reports publication, Stephenson et al. visualized and quantified changes in lipid metabolism in human induced pluripotent stem cell (iPSC)-derived microglia during immune activation. Biotium’s LipidSpot™ 488 Lipid Droplet Stain was used to detect changes in intracellular lipid droplets in response to lipopolysaccharide (LPS) and amyloid-beta exposure. This allowed the researchers to map lipid droplet accumulation and confirm its significant role in microglial immune signaling. Figure 1 below (courtesy of Stephenson, R.A.) shows an example of microglial staining using Biotium’s red fluorescent LipidSpot™ 610 from a related study.
Credit: Stephenson, R.A.
The authors also discovered that inhibition of triglyceride biosynthesis prevented LPS-induced microglial phagocytosis. Biotium’s ViaFluor® 488 SE was used as a reference cytoplasmic stain in the phagocytosis monitoring assay.
The study showed that pharmacological inhibition of triglyceride synthesis restored homeostatic gene expression, reduced NF-κB translocation, and improved surveillance deficits in APOE4-expressing microglia. Biotium’s lipid-specific and cytoplasmic fluorescent tools were instrumental in visualizing dynamic cellular changes. These discoveries highlight the potential of targeting lipid droplet metabolism to rebalance microglial immune function in Alzheimer’s disease.
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Full Citation:
Stephenson, R. A., Sepulveda, J., Johnson, K. R., Lita, A., Gopalakrishnan, J., Acri, D. J., Beilina, A., Cheng, L., Yang, L. G., Root, J. T., Ward, M. E., Combs, C., Skarnes, W. C., Cookson, M. R., Shih, H. Y., Larion, M., Rebeck, G. W., & Narayan, P. S. (2025). Triglyceride metabolism controls inflammation and microglial phenotypes associated with APOE4. Cell Reports, 44(7), 115961. https://doi.org/10.1016/j.celrep.2025.115961