Maternal Eicosapentaenoic Acid Feeding Decreases Placental Lipid Deposition and Improves the Homeostasis of Oxidative Stress Through a Sirtuin-1 (SIRT1) Independent Manner

Abstract

Scope: Maternal obesity has been associated with increased placental lipotoxicity and impaired mitochondrial function. Sirtuin-1 (SIRT1) is an important regulator of both lipid metabolism and mitochondrial biogenesis. The present study aims to determine whether supplementation of the maternal diet with eicosapentaenoic acid (EPA) can decrease placental lipid deposition and improve antioxidant ability, in a SIRT1-dependent manner.

Methods and results: Pregnant SIRT1^+/- mice (mated with male SIRT1^+/- ) are fed a high-fat diet consisting of 60% of the kcal from fat, or an equienergy EPA diet for 18.5 d. Supplementation with EPA significantly changes maternal plasma, placental and fetal fatty acid composition, and decreases placental and fetal lipid content. In addition, placental antioxidant capacity and lipid peroxidation products are increased, placental uncoupling protein 1 (UCP1) and PPARγ coactivator-1 α (PGC1α) expression are activated, and mitochondrial swelling decreases. While SIRT1 deficiency has little effect on placental fatty acid composition and lipid content, decreased fetal lipid deposition is observed, placental PGC1α expression decreases, mitochondrial swelling increases, and placental total superoxide dismutase (T-SOD) activity increases. Both EPA and SIRT1 have no effect on BODIPY-FL-C16 uptake. Interestingly, there is no significant interaction between diet and genotype.

Conclusion: Maternal EPA feeding decreases placental lipid deposition and improves placental oxidative stress homeostasis independent of SIRT1.

Keywords: Mitochondria; PGC1; SIRT1; oxidative stress; placental lipotoxicity.