Conclusion
Free radical-derived oxysterols accumulate in the "diabetic" fat and may act as novel adipokines modulating the adipogenic potential of undifferentiated adipose precursor cells.
Results
7-ketocholesterol (7κ-C) and 7β-hydroxycholesterol were unambiguously detected in adipocytes, which showed higher oxysterol accumulation (P < .01) in OBT2D, as compared with CTRL individuals. Notably, the accumulation of oxysterols in adipocytes was predicted by the adipose cell size of the donor (R2 = 0.582; P < .01). Challenging ASCs with free radical-derived type I (7κ-C) and type II (5,6-Secosterol) oxysterols led to a time- and concentration-dependent decrease of cell viability. Meaningfully, at a non-toxic concentration (1μM), these bioactive lipids hampered adipogenic differentiation of ASCs by sequential activation of WNT/β-catenin, p38-MAPK, ERK1/2, and JNK signaling pathways.