Vitamin D Modulates Lipid Composition of Adipocyte-Derived Extracellular Vesicles Under Inflammatory Conditions

Scope: Adipocyte-derived extracellular vesicles (AdEVs) convey lipids that can play a role in the energy homeostasis. Vitamin D (VD) has been shown to limit the metabolic inflammation as it decreases inflammatory markers expression in adipose tissue (AT). However, VD effect on adipocytes-derived EVs has never been investigated.Methods and results: Thus, the aim of this study is to evaluate the AdEVs lipid composition by LC-MS/MS approach in 3T3-L1 cells treated with VD or/and pro-inflammatory factor (tumor necrosis factor alpha [TNF alpha]). Among all lipid species, four are highlighted (glycerolipids, phospholipids, lysophospholipids, and sphingolipids) with a differential content between small (sEVs) and large EVs (lEVs). This study also observes that VD alone modulates EV lipid species involved in membrane fluidity and in the budding of membrane. EVs treated with VD under inflammatory conditions have different lipid profiles than the control group, which is more pronounced in lEVs. Indeed, 25 lipid species are significantly modulated in lEVs, compared with only seven lipid species in sEVs.Conclusions: This study concludes that VD, alone or under inflammatory conditions, is associated with specific lipidomic signature of sEVs and lEVs. These observations reinforce current knowledge on the anti-inflammatory effect of VD. The adipocyte-derived extracellular vesicles convey lipids that could play a role in the energy homeostasis. It has been shown that vitamin D limit the metabolic inflammation by decreasing inflammatory markers expression in adipose tissue. This study demonstrated that vitamin D alone or in inflammatory condition induced by TNF alpha are associated with specific lipid signature of small and large extracellular vesicles from adipocyte. The current study provided a new perspective in the anti-inflammatory action of vitamin D.image