Assesing the effect of Ursolic Acid on Lipid Droplet biogenesis using a Langmuir model system

B. CARUSO; THOME J; WILKE N; DELGUI L

Congreso; XLVIII REUNION SAB; 2019

According to the latest Lipid Droplet (LD) biogenesis models, interfacial tension plays acritical role on such process, determining the shape of the budding LD from the ER. Wehave previously presented triglyceride (TG) ?lenses? at the air-water interface as a modelsystem for studying LD biogenesis. The performance of Langmuir monolayers of mixedphosphatidylcholine (EPC)/TG in coexistence with TG microlenses (i.e. an excluded TGphase floating in the surface) and the characterization of their lenses´ thickness byBrewster Angle Microscopy (BAM) allow evaluating the proneness of TG lenses to form aLD. This is done by characterizing the associated thermodynamics and the resultingshape of the TG lenses. Here, we evaluated the modulation of TG lenses tendency todetach from the interface by the presence of a third component with interfacial activity.For this purpose, we choose Ursolic Acid (UA), a natural pentacyclic triterpenoid withmany biological effects and a clear interfacial activity. We found that UA slightlydiminished the surface pressure at which TG phase separation occurs (i.e., lensesappearance) in composition dependent manner (both %UA and PC/TG relation). Sucheffect may be correlated with the dependency of UA interfacial partitioning on lipidcomposition. On the other hand, BAM analysis showed a lower reflectivity of lenses in thepresence of UA. Assuming a negligible effect of UA on the refractive index of TG lenses,this implies a thinning of such structures. Additionally, the decreased radii of lensesobserved allowed us concluding that the contact angle of the lenses is lower in thepresence of UA. In conclusion, this experimental model allowed the detection of aninterfacial active compound, like UA, affecting both the energy necessary to form the TGlenses and its shape, leading to structures of lower curvature and radii. These results arein accordance with observed effects of UA on LD in cells: a decrease in LD number andradii.