Obesity downregulates lipid metabolism genes in first trimester placenta

Placentas of obese women have low mitochondrial beta-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Maternal fasting triglyceride and insulin levels were measured in plasma collected at the time of procedure. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPK alpha), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. Placental ACOX1 protein was higher in women with obesity and correlated with maternal circulating triglycerides. The PPAR alpha pathway was enriched for placental genes impacted by obesity, and PPAR alpha antagonism significantly reduced H-3-palmitate oxidation in 1(st) trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy.

Automated summary

Placentas of obese women show impaired fatty acid metabolism and lipid accumulation from early pregnancy. The expression of genes associated with fatty acid oxidation, uptake, synthesis, and storage is reduced in these placentas, particularly in placentas of male fetuses. The PPAR alpha pathway is impacted by obesity and PPAR alpha antagonism reduces fatty acid oxidation in 1st trimester placental explants.