Maternal and fetal lipid metabolism under normal and gestational diabetic conditions

Abstract

Maternal lipids are strong determinants of fetal fat mass. Here we review the overall lipid metabolism in normal and gestational diabetes mellitus (GDM) pregnancies. During early pregnancy, the increase in maternal fat depots is facilitated by insulin, followed by increased adipose tissue breakdown and subsequent hypertriglyceridemia, mainly as a result of insulin resistance (IR) and estrogen effects. The response to diabetes is variable as a result of greater IR but decreased estrogen levels. The vast majority of fatty acids (FAs) in the maternal circulation are esterified and associated with lipoproteins. These are taken up by the placenta and hydrolyzed by lipases. The released FAs enter various metabolic routes and are released into fetal circulation. Although these determinants are modified in maternal GDM, the fetus does not seem to receive more FAs than in non-GDM pregnancies. Long-chain polyunsaturated FAs are essential for fetal development and are obtained from the mother. Mitochondrial FA oxidation occurs in fetal tissue and in placenta and contributes to energy production. Fetal fat accretion during the last weeks of gestation occurs very rapidly and is sustained not only by FAs crossing the placenta, but also by fetal lipogenesis. Fetal hyperinsulinemia in GDM mothers promotes excess accretion of adipose tissue, which gives rise to altered adipocytokine profiles. Fetal lipoproteins are low at birth, but the GDM effects are unclear. The increase in body fat in neonates of GDM women is a risk factor for obesity in early childhood and later life.

Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring

“…Our in vitro results confirm that AMSCs exposed to high concentrations of insulin, glucose and palmitic acid, simulating the hyperinsulinemia, hyperglycemia, and dyslipidemia observed in metabolic syndrome 40 but also in pregnancies complicated by diabetes, 41 reproduced the inflammatory expression profile, the migration capacity, and the chemotactic activity observed in GDM-derived AMSCs.…”

Postprandial Triglycerides Predict Newborn Fat More Strongly than Glucose in Women with Obesity in Early Pregnancy

“…Maternal IR in OB increases maternal lipolysis, elevating FTGs and FFAs (31,33). Because the fetus has a limited capacity for de novo lipogenesis and fatty acid oxidation, excess maternal TGs can be hydrolyzed to FFAs by placental lipases for fetal fat accretion (14,(33)(34)(35). Although the high insulin levels generated by women with OB suppressed PP FFAs to levels similar to those in women with NW, the early FTGs and PPTGs in women with OB were already as high as those in mothers with NW later in pregnancy ( Figure 1A), providing early fetal-placental exposure to excess lipids (36).…”

The influence of placental metabolism on fatty acid transfer to the fetus

“…However, the placenta does express genes for enzymes that can release fatty acids from acylCoA, triglyceride, and phospholipid pools (18,21). It has been suggested that glucose and fatty acid transfer may occur preferentially in regions of vascular syncytial membrane where diffusion distance is low and metabolism may be limited (22).…”