Evidence of a DHA signature in the lipidome and metabolome of human hepatocytes

Cell supplementation with bioactive molecules often causes a perturbation in the whole intracellular environment. Omics techniques can be applied for the assessment of this perturbation. In this study, the overall effect of docosahexaenoic acid (DHA) supplementation on cultured human hepatocyte lipidome and metabolome has been investigated using NMR in combination with traditional techniques. The effect of two additional bioactives sharing with DHA the lipid lowering effect - propionic acid (PRO) and protocatechuic acid (PCA) - has been also evaluated, also considering possible synergism. NMR analysis of the cell lipid extracts showed that DHA supplementation, alone or in combination with PCA or PRO, strongly altered the cell lipid profile. The perfect discrimination between cells receiving DHA (alone or in combination) and the other cells reinforced the idea of a global rearrangement of the lipid environment induced by DHA. Notably, GC and fluorimetric analyses totally confirmed the strong discrimination obtained by NMR. The DHA signature was evidenced not only in the cell lipidome, but also in the metabolome. Results herein reported indicate that NMR, combined with other techniques, represents a fundamental approach while studying the effect of the supplementation of bioactives, particularly in the case of molecules having a broad spectrum of mechanisms of action.