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

During the first two-thirds of gestation, the mother is in an anabolic cond ition, increasing her fat depots thanks to both hyperphagia and enhanced li pogenesis. During the last third of gestation, the mother switches to a cat abolic condition. Glucose is the mast abundant nutrient crossing the placen ta, which causes maternal hypoglycemia despite an increase in the gluconeog enetic activity. Adipose tissue lipolytic activity becomes enhanced, increa sing plasma levels of FFA and glycerol that reach the liver; consequently t here is an enhanced production of triglycerides that return to the circulat ion in the form of very low density lipoproteins (VLDL). Glycerol is also u sed as a preferential gluconeogenetic substrate, saving other more essentia l substrates, like amino acids, far the fetus. Under fasting conditions, fatty acids are converted into ketone bodies thro ughout the beta-oxidation pathway, and these compounds easily cross the pla cental barrier and are metabolized by the fetus. An enhanced liver producti on of VLDL-triglycerides together with a decrease in adipose tissue lipopro tein lipase (LPL) and an increase in plasma activity of cholesterol ester t ransfer protein causes both an intense increment in these lipoproteins and a proportional enrichment of triglycerides in both low and high density lip oproteins. Maternal triglycerides do not cross the placenta, but the presen ce 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 indu ction of LPL activity in the mammary glands, driving circulating triglyceri des to this organ for milk synthesis, allowing essential fatty acids derive d from the mother's diet to become available to the suckling newborn.