Endothelial Lipid Droplets as Potential Intermediates in Fatty Acid Transport from Blood to Parenchymal Tissue

The transport of dietary fatty acids (FAs) from the bloodstream to peripheral tissues is essential for energy homeostasis, yet the intracellular mechanisms by which FAs traverse endothelial cells remain incompletely understood. Endothelial lipid droplets (LDs), traditionally viewed as intracellular lipid storage organelles, have recently emerged as dynamic regulators of lipid metabolism and may serve as intermediates in endothelial FA trafficking. This study investigated whether endothelial LDs function as transient intermediates in the transport of FAs from the circulation to parenchymal tissues. Endothelial-specific adipose triglyceride lipase knockout (Atgl ECKO) mice and wild-type (WT) controls were administered BODIPY FL C16, a fluorescently labeled fatty acid, by oral gavage following a six-hour fast. Plasma samples and multiple tissues were collected at defined time points for fluorescence analysis using confocal microscopy and blood chemistry assays. Whole-mount imaging demonstrated successful uptake and localization of BODIPY-labeled FAs in epididymal white adipose tissue, brown adipose tissue, and skeletal muscle, validating the use of BODIPY FL C16 as an in vivo tracer of FA transport. Plasma triglyceride and BODIPY fluorescence measurements revealed no significant differences between WT and Atgl ECKO mice at early time points but demonstrated significant differences at three hours following gavage. These findings suggest that endothelial ATGL deficiency alters postprandial FA transport and are consistent with the hypothesis that endothelial LDs contribute to intracellular FA trafficking. Although additional experiments are required to establish a direct mechanistic role for LDs, this work provides preliminary evidence supporting their potential function as intermediates in endothelial FA transport and highlights a possible new mechanism regulating lipid delivery to peripheral tissues.