Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus

Abstract

During the first two-thirds of gestation, the mother is in an anabolic condition, increasing her fat depots thanks to both hyperphagia and enhanced lipogenesis. During the last third of gestation, the mother switches to a catabolic condition. Glucose is the most abundant nutrient crossing the placenta, which causes maternal hypoglycemia despite an increase in the gluconeogenetic activity. Adipose tissue lipolytic activity becomes enhanced, increasing plasma levels of FFA and glycerol that reach the liver; consequently there is an enhanced production of triglycerides that return to the circulation in the form of very low density lipoproteins (VLDL). Glycerol is also used as a preferential gluconeogenetic substrate, saving other more essential substrates, like amino acids, for the fetus. Under fasting conditions, fatty acids are converted into ketone bodies throughout the beta-oxidation pathway, and these compounds easily cross the placental barrier and are metabolized by the fetus. An enhanced liver production of VLDL-triglycerides together with a decrease in adipose tissue lipoprotein lipase (LPL) and an increase in plasma activity of cholesterol ester transfer protein causes both an intense increment in these lipoproteins and a proportional enrichment of triglycerides in both low and high density lipoproteins. Maternal triglycerides do not cross the placenta, but the presence of LPL and other lipases allows their hydrolysis, releasing fatty acids to the fetus. Under fasting conditions, the maternal liver uses circulating triglycerides as ketogenic substrates. Around parturition there is an induction of LPL activity in the mammary glands, driving circulating triglycerides to this organ for milk synthesis, allowing essential fatty acids derived from the mother's diet to become available to the suckling newborn.

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

“…Maternal non-esterified FA (NEFA) released from lipolysis are mainly re-esterified into TAG in the liver, and these are released into the circulation in the form of VLDL. There is an increase in plasma TAG concentration during late gestation and this is termed the hypertriacylglycerolemia of pregnancy 68 . Also, during late pregnancy levels of TAG increase in LDL and HDL probably associated with increased activity of the cholesteryl ester transfer protein (CETP) (ref.…”

“…During the first two trimesters fetal growth is limited and the mother accumulates nutrients and energy in her body stores. The last trimester is characterised by a catabolic phase whereby maternal adipose tissue lipolysis releases FA to the maternal circulation which will be transferred to the fetus through the placenta 68 . Maternal non-esterified FA (NEFA) released from lipolysis are mainly re-esterified into TAG in the liver, and these are released into the circulation in the form of VLDL.…”

Archaeological Starch

“…This glucose requirement is normally met from dietary carbohydrates and gluconeogenesis from non-carbohydrate sources (e.g., the glycerol moiety of triglycerides, some amino acids), or absorption of short chain fatty acids such as propionate produced in fermentations by gut microflora in the colon [89]. Glucose is the main energy source for foetal growth and low glucose availability can compromise foetal survival [90,91].…”

Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

“…Thus we hypothesize that PPARγ may be an important contributor to the metabolic adaptations required in adipose tissue during pregnancy and may regulate insulin sensitivity. Here we studied the role of PPARγ2 in the metabolic adaptations associated with the last phase of pregnancy in mice when a state of IR is established (16).…”