Saturated free fatty acids induce placental trophoblast lipoapoptosis

Abstract

Introduction Obesity during pregnancy increases the risk for maternal complications like gestational diabetes, preeclampsia, and maternal inflammation. Maternal obesity also increases the risk of childhood obesity, intrauterine growth restriction (IUGR) and diabetes to the offspring. Increased circulating free fatty acids (FFAs) in obesity due to adipose tissue lipolysis induces lipoapoptosis to hepatocytes, cholangiocytes, and pancreatic-β-cells. During the third trimester of human pregnancy, there is an increase in maternal lipolysis and release of FFAs into the circulation. It is currently unknown if increased FFAs during gestation as a result of maternal obesity cause placental cell lipoapoptosis. Increased exposure of FFAs during maternal obesity has been shown to result in placental lipotoxicity. The objective of the present study is to determine saturated FFA-induced trophoblast lipoapoptosis and also to test the protective role of monounsaturated fatty acids against FFA-induced trophoblast lipoapoptosis using in vitro cell culture model. Here, we hypothesize that saturated FFAs induce placental trophoblast lipoapoptosis, which was prevented by monounsaturated fatty acids. Methods Biochemical and structural markers of apoptosis by characteristic nuclear morphological changes with DAPI staining, and caspase 3/7 activity was assessed. Cleaved PARP and cleaved caspase 3 were examined by western blot analysis. Results Treatment of trophoblast cell lines, JEG-3 and JAR cells with palmitate (PA) or stearate (SA) induces trophoblast lipoapoptosis as evidenced by a significant increase in apoptotic nuclear morphological changes and caspase 3/7 activity. We observed that saturated FFAs caused a concentration-dependent increase in placental trophoblast lipoapoptosis. We also observed that monounsaturated fatty acids like palmitoleate and oleate mitigates placental trophoblast lipoapoptosis caused due to PA exposure. Conclusion We show that saturated FFAs induce trophoblast lipoapoptosis. Co-treatment of monounsaturated fatty acids like palmitoleate and oleate protects against FFA-induced trophoblast lipoapoptosis.

Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques

“…Additionally, pathways associated with the production of the monosaturated fatty acid palmitoleate were increased in the microbiome of pregnant individuals. Palmitoleate has been shown to play an important role in the maintenance of placental trophoblasts by preventing apoptosis ( 48 ). We also observed increased enrichment of GO terms associated with the transportation of simple sugars like lactate, glucose, and galactose in late pregnancy compared to the GO terms in postpartum samples.…”

Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study

“…Figure 4 presents volcano plots of the odds ratio (OR) distributions for each maternal metabolite according to the faltering growth and early accelerating growth phenotypes estimated from logistic regression analysis, adjusted for maternal age and newborn sex. These phenotypes were associated with 709 statistically significant maternal metabolites with positive effect for the faltering growth phenotype and 54 metabolites (appendix pp [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] for the early accelerating growth phenotype, and 31 statistically significant maternal metabolites with negative effect for the faltering growth phenotype and 76 metabolites (appendix pp 43-45) for the early accelerating growth phenotype (figure 4A and B). 33 metabolites (appendix p 46) overlapped between the falter ing growth and early accelerating growth phenotypes, which were also associated with 627 (for the faltering growth phenotype) and 1675 (for the early accelerating growth phenotype) statistically significant umbilical cord venous metabolites with positive effect.…”

Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis

“…Palmitoleate decreases fat deposition in the liver and enhances insulin sensitivity [57]. Studies have shown that palmitoleate protects against free fatty acid-induced hepatocyte lipoapoptosis [23] and trophoblast lipoapoptosis [59], respectively. Supplementation of palmitoleate has shown to be effective against non-alcoholic fatty liver disease and atherosclerosis in mouse models [60,61].…”