Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet

Abstract

Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21–22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer was assessed in rodent and human samples by quantitative real time polymerase chain reaction. In rats, placental mRNA expression of ApoA2, ApoC2, Cubn, Fgg, Mttp and Ttr was significantly elevated (3–30 fold) in animals fed a high LA (36% fat) diet, suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer inconsistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of genes associated with cholesterol transport in a rat model. This may contribute to altered fetal development and potentially programme disease risk in later life. Further investigation of human placenta in response to specific dietary interventions is required.

Maternal High Linoleic Acid Alters Placental Fatty Acid Composition

“…The placental labyrinth zone is key for maternal/fetal exchange and a key finding of this study is that a high maternal LA diet alters expression of nutrient transporters in placental labyrinth at gestation day 20. Recent studies have investigated the effect of different concentrations of LA in the maternal diet on placental weight, fatty acid composition and expression of genes associated to cholesterol transport and packaging [ 13 , 29 ]. However, to the best of our knowledge, this is the first study to investigate the effect of a high maternal LA diet on nutrient transport and angiogenesis associated genes.…”

“…At this time, there has been limited investigations on the capacity of LA to alter placental function. A recent study demonstrated that a high LA diet altered the placental expression of cholesterol packaging and transport genes in the rodent [ 13 ]. In this study, there was an elevated content of fat, which may have contributed to the changes observed.…”

The Expanding Role of Mitochondria, Autophagy and Lipophagy in Steroidogenesis

“…However, instead of StAR, the human placenta express MLN64 (metastatic lymph node 64 protein), which has a C-terminal domain homologous to StAR [33,34]. Many studies have shown that the cholesterol binding domain of both proteins in human have similar biophysical and functional properties and are able to support steroidogenesis in placental tissue and their cell derivatives in different species [37][38][39][40][41][42][43][44][45][46][47][48].…”

Early life programming of health and disease: The long‐term consequences of obesity in pregnancy

“…109 Similarly, the observation that expression of genes that regulate placental cholesterol transport is related to maternal BMI suggests that cholesterol handling is disrupted by maternal obesity. 110 This may promote atherogenesis in the placental vessels (associated with pre-eclampsia) and disrupt steroid hormone production. Obesity impacts upon fatty acid transport by the placenta and promotes an inflammatory response.…”