Size of lipid emulsion droplets influences metabolism in human CD4+ T cells

• Published in: Biochemical and biophysical research communications 2024-11, Vol.733, p.150680, Article 150680
• Main Authors: Noureddine, Nazek, Holtzhauer, Gregory, Wawrzyniak, Paulina, Srikanthan, Pakeerathan, Krämer, Stefanie D., Rogler, Gerhard, Lucchinetti, Eliana, Zaugg, Michael, Hersberger, Martin
• Format: Article
• Language: English
• Subjects: CD4+ T cells; Macropinocytosis; Nano-sized lipid emulsions; Total parenteral nutrition; β-oxidation
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.150680

Triglyceride-based lipid emulsions are critical for total parenteral nutrition (TPN), but their long-term use has adverse effects, such as severe liver dysfunction necessitating improved formulations. This study compares the uptake mechanism and intracellular fate of novel glycerol-stabilized nano-sized lipid emulsions with conventional emulsions in CD4+ T cells, focusing on their impact on cellular metabolism. Nanoemulsions were formulated with increased glycerol content. Uptake of emulsions in primary human CD4+ T cells was investigated using different endocytic blockers, then quantified by flow cytometry, and visualized by confocal microscopy. To investigate emulsion intracellular fate, fatty acids in membrane phospholipids were quantified by GC-MS/MS and cellular metabolism was assessed by Seahorse technology. Results show T cells internalize both conventional and nano-sized emulsions using macropinocytosis. Fatty acids from emulsions are stored as neutral lipids in intracellular vesicles and are incorporated into phospholipids of cellular membranes. However, only nanoemulsions additionally use clathrin-mediated endocytosis and deliver fatty acids to mitochondria for increased β-oxidation. Size of lipid emulsion droplets significantly influences their uptake and subsequent metabolism in CD4+ T cells. Our results highlight the potential for improved nutrient utilization with nanoemulsions in TPN formulations possibly leading to less adverse effects. [Display omitted] •Triglyceride-based lipid emulsions are critical for total parenteral nutrition (TPN), but their uptake in CD4+ T cells has not been investigated.•Fatty acids from emulsions are taken up in T cells by macropinocytosis, are stored as neutral lipids, and are incorporated into phospholipids.•Nanoemulsions are additionally taken up by clathrin-mediated endocytosis and deliver fatty acids to mitochondria for increased β-oxidation.•Results highlight the potential for improved nutrient utilization with nanoemulsions in TPN formulations possibly leading to less adverse effects.