ArticleProceedings of the National Academy of Sciences of the United States of America2012
Functional roles of fructose.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 113 citations in OpenAlex.
- Uterine histotroph and conceptus development. IV. Metabolomic analyses of uterine luminal fluid reveals regulatory landscapes during the peri-implantation period of pregnancy in pigs†.Biology of reproduction · 2025Article
- Uterine histotroph and conceptus development. V. Comparative analyses of arginine-mediated transcriptomic reprogramming in conceptus trophectoderm of pigs and sheep†.Biology of reproduction · 2025Article
- Effects of Maternal Nutrition and One-Carbon Metabolite Supplementation on Fetal Jejunal Morphology and Hexose Transporter Expression in Beef Cattle.Veterinary sciences · 2025Article
- Conceptus Elongation, Implantation, and Early Placental Development in Species with Central Implantation: Pigs, Sheep, and Cows.Biomolecules · 2025Review
- Key biochemical pathways during pregnancy in livestock: mechanisms regulating uterine and placental development and function.Reproduction & fertility · 2025Review
- A Preliminary Study on the Qualitative and Quantitative Changes of Amino Acids in Whole Apple, Apple Peel, and Flesh Samples Grown in Lithuania.Plants (Basel, Switzerland) · 2025Article
- Metabolic reprogramming and epigenetic effects due to reducing sugars and glycation products in cancer.Frontiers in epigenetics and epigenomics · 2025Review
- Effect of maternal and post-weaning dietary chitosan oligosaccharide supplementation on reproductive performance of sow and gut growth and development in offspring.Frontiers in veterinary science · 2025Article
- Compatibility and stability of ademetionine 1,4-butanedisulfonate injection mixed with fructose and glucose diluents and pilot study of long-term storage impurities by LC-MS/MS.Scientific reports · 2024Article
- Maternal Malnutrition and Elevated Disease Risk in Offspring.Nutrients · 2024Review
- Article
- Rate of body weight gain during early gestation in F0 beef heifers has effects that extend multigenerationally to the F2 fetuses.Journal of animal science · 2024Article
- Fructose metabolism is unregulated in cancers and placentae.Experimental biology and medicine (Maywood, N.J.) · 2024Review
- Fructose might be a clue to the origin of preeclampsia insights from nature and evolution.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Review
- Maternal Fructose Intake, Programmed Mitochondrial Function and Predisposition to Adult Disease.International journal of molecular sciences · 2022Review
- Progesterone Induces Apoptosis and Steroidogenesis in Porcine Placental Trophoblasts.Animals : an open access journal from MDPI · 2022Article
- Fructose metabolism and its role in pig production: A mini-review.Frontiers in nutrition · 2022Review
- A Role for Fructose Metabolism in Development of Sheep and Pig Conceptuses.Advances in experimental medicine and biology · 2022Article
- Maternal Heat Stress Alters Expression of Genes Associated with Nutrient Transport Activity and Metabolism in Female Placentae from Mid-Gestating Pigs.International journal of molecular sciences · 2021Article
- Capture and metabolomic analysis of the human endometrial epithelial organoid secretome.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the periimplantation period of pregnancy, pig blastocysts undergo morphological changes and differentiation requiring secretion and transport of nutrients (histotroph) into the uterine lumen. Of these nutrients, glucose is converted to fructose, an isomer of glucose, by conceptus trophectoderm. Although glucose is an energy source for proliferation and growth of mammalian cells, the role of fructose in uterine histotroph is unclear although it is the most abundant hexose sugar in fetal blood and fluids of ungulate mammals (e.g., cows, sheep, and pigs). In this study, we used porcine trophectoderm cells to determine that fructose increased cell proliferation, as did glucose. Western blot analyses of porcine trophectoderm cell extracts revealed that fructose increased the abundance of phosphorylated-RPS6K, -EIF4EBP1, and -RPS6 over basal levels within 30 min, and those levels remained elevated to 120 min. Phosphorylation of both RPS6K and EIF4EBP1 proteins in response to fructose was inhibited by inhibitors of both PI3K and MTOR. Further, when we investigated the inhibition of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) by azaserine (an inhibitor of GFPT1) and GFPT1 siRNA, we found that MTOR-RPS6K and MTOR-EIF4EBP1 signaling in response to fructose is mediated via GFPT1 activation and the hexosamine pathway. We further demonstrated that fructose stimulates the production of hyaluronic acid via GFPT1 and the hexosamine biosynthesis pathway. Collectively, these results demonstrate critical roles for fructose that are mediated via the hexosamine biosynthesis pathway to stimulate MTOR cell signaling, proliferation of porcine trophectoderm cells, and synthesis of hyaluronic acid, a significant glycosaminoglycan in the pregnant uterus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.