Introduction: Maternal gestational obesity is associated with increased activities of fatty acid (FA) desaturase enzymes as well as impairments in mitochondrial respiratory function in the term placenta. Recently, maternal diet independent from measures of maternal body composition has been highlighted as a potential mediator of placental metabolic function. However, the extent to which dietary fats modulate FA desaturase enzyme activity and oxidative metabolism is poorly understood. We postulated that a prolonged dietary saturated FA exposure would negatively impact BeWo trophoblast respiratory activity and promote FA desaturase enzyme activity.
Methods: BeWo cells were cultured for 72 H in F12K media supplemented with 100 µM palmitate (PA), oleate (OA) or a 1:1 combination of PA+OA (P/O) conjugated 2:1 to Bovine Serum Albumin (BSA, 0.3%). Mitochondrial activity was determined via Seahorse Mito Stress Test. Lipids were isolated using chloroform-methanol extraction and analyzed using gas chromatography coupled with flame ionization detection. FA were identified through comparison of retention times with known standards. Fatty acid desaturation enzyme activity (SCD-1, FADS1, FADS2) was determined with desaturation indices (ratio of enzyme product to substrate). A randomized block design ANOVA was utilized for statistical analyses.
Results: PA and P/O treatment increased basal and maximal respiratory activity. PA treatment increased the C16:1n7/C16:0 index (SCD-1 activity) while OA and P/O treatment decreased the C16:1n7/C16:0 index. Additionally, OA and P/O treatment was associated with an increased C18:3n6/C18:2n6 index (FADS2 activity). There were no significant differences in the C20:4n6/C20:3n6 indices (FADS1 activity).
Conclusion: The PA-mediated increases in respiratory activity may precede and contribute to the development of diet-mediated placental mitochondrial impairments. The dietary-FA associated alterations in desaturase enzyme activity alters the availability of lipid substrates for oxidation and potentially promotes failures in placental energy production. Overall, these results demonstrate that dietary fats alone are important regulators of placental mitochondrial function and desaturase enzyme activity.
Ousseynou Sarr– Research Associate, Department of Physiology and Pharmacology, Western University.
Timothy Regnault– Associate Professor, Department of Physiology and Pharmacology, Lawson Health Research Institute, Children’s Health Research Institute.