Inducible lipid storage and steatosis in the human choroid plexus associated with age and adiposity
Espericueta, N. V.; Neel, M. J.; Wang, Y.; Soo, T. J.; Porahang, P.; Goyokpin, F. A.; Salehi, R. S.; Khan, S.; Lee, J.; Maramica, N. B.; Flores, G.; Kulkarni, A.; Plaha, S. S.; Ghahremani, S.; Huang, W.; Smith, Q.; Chang, P.; Johnson, B. A.; Monuki, E. S.
Show abstract
Cells that store lipids for other cells or organs can contain "giant" or large lipid droplets (LLDs) greater than 2 {micro}m in diameter. In this study, human postmortem choroid plexus was evaluated for lipid droplets. Staining with hematoxylin and eosin (H&E), the lipophilic dye Oil red O, and anti-adipophilin antibodies established the presence of LLDs exceeding 10 {micro}m in diameter in choroid plexus epithelial cells (CPECs). Manual annotation of H&E stains from 105 cases revealed a significant association between age and the percentage of CPECs containing LLDs (reaching up to 69%) and involving LLDs in our largest annotated category (>5 {micro}m in diameter). The LLD association with age was replicated and extended to a total of 245 cases using a trained convolutional neural network, which further showed significant associations with body mass index at time of death (increasing with BMI), sex (higher in females >65 years old), and a near-significant association with Alzheimers Disease (lower in AD). Like HepG2 and derived hepatocytes, excess fatty acids in culture media readily induced LLDs and steatosis in human embryonic stem cell-derived CPECs. Akin to hepatocytes for the human body, we propose that CPECs store lipids for the human brain and become steatotic in the setting of excess adiposity.
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