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.
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In the last trimester, anti-insulin hormones, growth factors, and cytokines released by the placenta produce an insulin resistance-like state, which is further exacerbated for those with excess weight, increased maternal age, polycystic ovarian syndrome, and family history of diabetes.
“In the last trimester, anti-insulin hormones, growth factors, and cytokines released by the placenta produce an insulin resistance-like state, which is further exacerbated for those with excess weight, increased maternal age, polycystic ovarian syndrome, and family history of diabetes [2, 3].”
From Evaluating Traditional Chinese Medicine and Herbal Products for the Treatment of Gestational Diabetes Mellitus (2019) · cites this paper as [2]
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- Authors
- Herrera, E.
- Affiliations
- Universidad San Pablo CEU (ES)
- Corresponding author
- Herrera, E
- ORCID
- Herrera, E
- Venue
- European Journal of Clinical Nutrition
- Published
- 2000-03-01
- Volume
- 54
- Issue
- S1
- Pages
- S47-S51
- ISSN
- 0954-3007 (ISSN-L)
- 1476-5640
- OpenAlex
- W2062955339
- Cited by
- 347
- References
- 50
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 15 · 2023: 16 · 2022: 23 · 2021: 17 · 2020: 14 · 2019: 12 · 2018: 26 · 2017: 17 · 2016: 27 · 2015: 23 · 2014: 13 · 2013: 10 · 2012: 13
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- placental nutrient transfer, lipogenesis, maternal hypoglycemia, gluconeogenesis, adipose tissue lipolysis, free fatty acids, VLDL, triglycerides, lipoprotein lipase, cholesteryl ester transfer protein, ketone bodies, fatty acid beta-oxidation, lactation, hyperphagia
- MeSH terms
- Adipose Tissue, Animals, Female, Fetus, Gluconeogenesis, Humans, Pregnancy, Carbohydrate Metabolism, Lipid Metabolism, Rats
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