Effect of Maternal Obesity on Placental Lipid Metabolism

Abstract

Obese women, on average, give birth to babies with high fat mass. Placental lipid metabolism alters fetal lipid delivery, potentially moderating neonatal adiposity, yet how it is affected by maternal obesity is poorly understood. We hypothesized that fatty acid (FA) accumulation (esterification) is higher and FA β-oxidation (FAO) is lower in placentas from obese, compared with lean women. We assessed acylcarnitine profiles (lipid oxidation intermediates) in mother-baby-placenta triads, in addition to lipid content, and messenger RNA (mRNA)/protein expression of key regulators of FA metabolism pathways in placentas of lean and obese women with normal glucose tolerance recruited at scheduled term Cesarean delivery. In isolated trophoblasts, we measured [3H]-palmitate metabolism. Placentas of obese women had 17.5% (95% confidence interval: 6.1, 28.7%) more lipid than placentas of lean women, and higher mRNA and protein expression of FA esterification regulators (e.g., peroxisome proliferator-activated receptor γ, acetyl-CoA carboxylase, steroyl-CoA desaturase 1, and diacylglycerol O-acyltransferase-1). [3H]-palmitate esterification rates were increased in trophoblasts from obese compared with lean women. Placentas of obese women had fewer mitochondria and a lower concentration of acylcarnitines, suggesting a decrease in mitochondrial FAO capacity. Conversely, peroxisomal FAO was greater in placentas of obese women. Altogether, these changes in placental lipid metabolism may serve to limit the amount of maternal lipid transferred to the fetus, restraining excess fetal adiposity in this population of glucose-tolerant women.

High‐fat diet intake modulates maternal intestinal adaptations to pregnancy and results in placental hypoxia, as well as altered fetal gut barrier proteins and immune markers

“…In humans, maternal HFD decreases levels of carnitine and short‐ and medium‐chain acylcarnitines in the placenta (Calabuig‐Navarro et al . ). We also show that maternal HFD significantly reduces placental carnitine (C0) and its acylcarnitine derivatives (C2, C3, C8 and C10).…”

Examination of the Lipid Profile in Pregnant Obese Women, Considering the Allele Status of the Genes of Angiotensin-Converting Enzyme (Ace I / D) and Plasminogen-1 (Pa-1 4g / 5g) Activator-Inhibitor

“…Impairment of lipid metabolism in women with obesity is found by many researchers 1,6,[9][10][11][12][13] . Increasing TC, LDL cholesterol, and TG with a decrease in HDL cholesterol are considered to be risk factors of perinatal complications, in particular placental dysfunction 2,[14][15][16][17][18][19] .…”

In Utero One‐Carbon Metabolism Interplay and Metabolic Syndrome in Cardiovascular Disease Risk Reduction

“…Further, using an in vitro perfusion system to study placental transfer of palmitic acid, researchers previously reported an elevated uptake and esterification of palmitate by human placenta . Indeed, research has shown a significant increase in lipogenesis and reduced fatty acid oxidation due to fewer mitochondria in placentas of woman with obesity as compared with lean women …”

“…[33][34][35] Offspring of overweight women are at a higher risk of developing obesity and associated complications such as cardiovascular diseases, in part, due to the role of the placenta in transferring nutrients such as FFAs to the developing fetus. [36][37][38] Indeed, evidence suggests that maternal obesity results in transfer of excess FFAs to the developing fetus, which may induce oxidative stress and inflammatory response, and in turn affect the epigenetic status of lipid sensing genes ( Figure 2). [33][34][35]39] This is believed to influence the early programming of the preadipocytes and insulin signaling in fetal tissues such as liver and heart.…”

“…[44] Indeed, research has shown a significant increase in lipogenesis and reduced fatty acid oxidation due to fewer mitochondria in placentas of woman with obesity as compared with lean women. [38] Key to this process is epigenetic regulation of genes involved in energy homeostasis including genes such as peroxisome proliferator-activated receptor (PPAR) isotypes. During the early stages of development, both PPAR-and PPAR-are known to play a role in follicular maturation, placental growth, as well as fetal FFAs substrate utilization.…”