Maternal high-fat-diet-induced placenta remodeling and gut microbiome shaping responsible for fetal liver lipid dysmetabolism

A maternal high-fat (HF) diet in utero may affect fetal development and cause metabolic problems during childhood and even adulthood. Diet-induced maternal obesity can impair gut barrier integrity and change gut microbiome, which may contribute to adverse placental adaptations and increase the obesity risk in offspring. However, the mechanism by which maternal obesity programming offspring metabolic disorder still need to be clarified. Methods: Female rats received a control diet or HF diet for 11 weeks before conception and during gestation. The placentas were collected on gestational day 21 before offspring delivery. Placental tissues, gut microbiome and short-chain fatty acids of dams and fetal liver tissues were studied. Results: Maternal HF diet altered the placental structure and metabolism-related transcriptome, including decreased G-protein-coupled receptor 43 expression. Furthermore, HF diet changed the gut microbiome and serum propionate level of dams. The fetal liver exhibited steatosis, enhanced oxidative stress, and increased expression of acetyl-CoA carboxylase 1 and lipoprotein lipase with maternal HF diet. Conclusions: HF diet intake during pregnancy shape gut microbiota and remodel placenta of dams, resulting in lipid dysmetabolism of fetal liver, which may ultimately contribute to the programming of offspring obesity.