Modulation of Fatty Acid Transport and Metabolism by Maternal Obesity in the Human Full-Term Placenta1

Abstract

Knowledge of the consequences of maternal obesity in human placental fatty acids (FA) transport and metabolism is limited. Animal studies suggest that placental uptake of maternal FA is altered by maternal overnutrition. We hypothesized that high maternal body mass index (BMI) affects human placental FA transport by modifying expression of key transporters. Full-term placentas were obtained by vaginal delivery from normal weight (BMI, 18.5-24.9 kg/m(2)) and obese (BMI > 30 kg/m(2)) women. Blood samples were collected from the mother at each trimester and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Lipoprotein lipase (LPL) activity was evaluated using enzyme fluorescence. In vitro linoleic acid transport was studied with isolated trophoblasts. Our results demonstrated that maternal obesity is associated with increased placental weight, decreased gestational age, decreased maternal high-density lipoprotein (HDL) levels during the first and third trimesters, increased maternal triglyceride levels during the second and third trimesters, and increased maternal T3 levels during all trimesters, and decreased maternal cholesterol (CHOL) and low-density lipoprotein (LDL) levels during the third trimester; and increased newborn CHOL, LDL, apolipoprotein B100, and T3 levels. Increases in placental CD36 mRNA and protein expression levels, decreased SLC27A4 and FABP1 mRNA and protein and FABP3 protein expression, and increased LPL activity and decreased villus cytotrophoblast linoleic acid transport were also observed. No changes were seen in expression of PPARA, PPARD, or PPARG mRNA and protein. Overall this study demonstrated that maternal obesity impacts placental FA uptake without affecting fetal growth. These changes, however, could modify the fetus metabolism and its predisposition to develop diseases later in life.

Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism

“…Additionally, obese women have an increased risk of giving birth to a very low birth weight baby (McDonald et al, 2010). Finally, no alteration of fetal weight by maternal obesity was reported in another study, but it was associated with a decrease in placental efficiency (Dubé et al, 2012).Biometry of the feto-placental unit has been obtained from different animal models of high maternal weight or obesity. Offspring from obese ewes increased their weight at mid-gestation whereas placentome weight was not altered (Zhu et al, 2009).…”

Effect of maternal obesity on pregnancy outcomes and long-term metabolic consequences

“…82 In addition, studies in human full-term placentas showed that maternal obesity impacts placental fatty acid uptake and could therefore modify the fetus metabolism and the child's predisposition to develop diseases later in life. 83 Maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress. 84 This environment via in utero programming may trigger adaptive pathways which ultimately result in increased percentage of body fat and propensity for future obesity in the offspring of obese women.…”

Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk

“…Placentas of obese women demonstrate decreased sodium-dependent neutral amino acid transporter (System A) expression (34) and, at least in vitro, IL-1β inhibited insulin-stimulated System A amino acid uptake in human placental trophoblast cells (35). Obese women show placental dysregulation of redox balance (36), decreased fatty acid transport, and increased placental lipoprotein lipase activity which could be responsible for placental triglycertides accumulation (37), although this contrasts to placenta-derived data from animal models studying diet-induced maternal obesity (see below).…”