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 (15–20 mm, control) and BFII (21–27 mm, 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‐α, and increased activation of inflammatory NF‐κB 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.