Free Fatty Acids from Type 2 Diabetes Mellitus Serum Remodel Mesenchymal Stem Cell Lipids, Hindering Differentiation into Primordial Germ Cells

Type 2 diabetes mellitus (T2DM) adversely affects the essential characteristics of adipose tissue-derived mesenchymal stem cells (AdMSCs). Given that T2DM is associated with an altered serum free fatty acid (FFA) profile, we examined whether diabetic serum FFAs influence the viability, differentiation, and fatty acid composition of the major lipid fractions of human AdMSCs in vitro. Serum FFAs were isolated from 7 diabetic and 10 healthy nondiabetic female individuals. AdMSCs were cultured and differentiated into primordial germ cell-like cells (PGCLCs) in the presence of either diabetic or nondiabetic FFAs. Cell viability was assessed using trypan blue staining. Cell differentiation was evaluated by measuring the PGCLC transcriptional markers Blimp1 and Stella. Lipid fractionation and fatty acid quantification were performed using thin-layer chromatography and gas–liquid chromatography, respectively. Both diabetic and nondiabetic FFAs significantly reduced the viability of PGCLCs. The gene expression of both differentiation markers was significantly lower in cells exposed to diabetic FFAs than in those treated with nondiabetic FFAs. Saturated fatty acids were significantly increased and linoleic acid was significantly decreased in the cellular phospholipid fraction after exposure to diabetic FFAs. In contrast, monounsaturated fatty acids were reduced and linoleic acid was elevated in the cellular triglyceride fraction in response to diabetic FFAs. Such an altered serum FFA profile in patients with T2DM reduces the proliferation and differentiation potential of AdMSCs, presumably due to the aberrant distribution of fatty acids into cell phospholipids and triglycerides. Graphical Abstract