Maternal obesity stimulates lipotoxicity and up-regulates inflammatory signaling pathways in the full-term swine placenta

This study aimed to investigate the effects of back-fat thickness (BF), at mating of sows, on placental lipotoxicity, oxidative stress, and inflammation. We performed iTRAQ labeling-based proteomic analysis on term placentas obtained by vaginal delivery from BFI (15-20mm, control) and BFII (21-27mm, obese) sows formed according to BF at mating. Proteomic analysis revealed 413 proteins to be significantly different in placenta from BFII sows by 1.2-fold. Gene ontology (GO) analysis identified proteins related to lipid metabolism and inflammatory response to be altered in placenta from obese sows. Indicative of a lipotoxic placental environment, increased placental lipid, and up-regulated mRNA expression of lipogenic genes, including ADRP (p=.06), PPARD, FASN, ACACA, DGAT1, and LIPIN3, were associated with decreased AMPK and increased activation of WNT signaling in placenta from BFII group (p<.05). Furthermore, we observed a 18% decrease in total antioxidant capacity (TAC), increased mRNA content of pro-inflammatory cytokines IL-6, IL-18, and TNF-, and increased activation of inflammatory NF-B and JNK signaling in placenta from BFII sows that was significantly associated with macrophage accumulation (p<.05). These findings suggest that maternal obesity aggravates a lipotoxic environment in pig term placenta that may be associated with placental dysfunction and impaired fetal growth.