Saturated and unsaturated fatty acids differentially regulate in vitro and ex vivo placental antioxidant capacity

Complications from prematurity are the leading cause of death among children under 5 years of age. Although clinical studies have shown a positive correlation between maternal high-fat diet (HFD) and preterm birth (PTB), the underlying mechanisms remain to be elucidated. Furthermore, it remains unclear how fatty acid type influences the effects of bacterial endotoxins.

HTR-8/SVneo trophoblasts were cultured in either 0.5 mmol L^-1 palmitic acid (PA) or linoleic acid (LA) in the absence or presence of 100 μg mL^-1 of lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Murine placental explants were cultured in either 2 mmol L^-1 PA or LA, and cell viability, total antioxidant capacity (TAC), lipid peroxidation, H₂ O₂ , heme oxygenase-1 (HO-1), and nuclear erythroid 2-related factor 2 (Nrf-2) and nuclear factor-kappa light-chain enhancer of activated B cells (NF-κB) transcription factor activity assays were assessed.

Palmitic acid significantly (i) increased cell death, (ii) decreased TAC, and (iii) increased lipid peroxidation; but did not significantly increase HO-1. In contrast, LA maintained cell viability and significantly increased TAC and HO-1. In addition, incubating placental explants with PA significantly increased NF-κB activity. Co-incubating cells with PA and LPS or LTA significantly potentiated H₂ O₂ production and increased lipid peroxidation. Co-incubating cells with PA and LTA synergistically impaired TAC, and LTA decreased TAC more so than LPS. Co-incubation with PA/LA and LPS/LTA decreased HO-1 levels compared to treatment with either fatty acid alone.

Our findings suggest that saturated and unsaturated fats differentially regulate placental viability, antioxidant capacity, and inflammation and the actions of gram-positive and gram-negative endotoxins.