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High fructose intake during pregnancy adversely affects insulin resistance, lipid profiles, and affects placental gene expression of nutrient transporters and angiogenesis in rat dams and their pregnant offspring

  • Author / Creator
    Song, Aleida LJH
  • Fructose intake has increased over the past several decades due to high consumption of sugary foods and drinks. In non-pregnant humans and animals, high fructose intake results in hyperlipidemia, insulin resistance and weight gain, although its effects on metabolic adaptations to pregnancy and on offspring have not been well-defined thus far. Three studies were conducted for this thesis with the overall purpose of assessing the effects of fructose intake on physiological changes related to pregnancy in dams and their pregnant offspring. In each study, female rats received a 10% fructose solution (FR) or distilled water (CONT) prior to and during pregnancy. Offspring remained on the same diet treatment as their mothers (Dams) prior to and during pregnancy. Glycemic control was assessed by measuring glucose and insulin concentrations throughout the study and an oral glucose tolerance test toward the end of pregnancy. Body weights and body composition were also measured. Gene expression for nutrient transporters and vascular development were measured in the placenta of Dams and Offspring. The first study compared the effects of fructose intake between pregnant and age-matched, non-pregnant rats (Dam-FR, n=6; NP-FR, n=5; Dam-CONT, n=4; NP-CONT, n=6). Dams and NP rats given fructose solution had increased concentrations of insulin (P=0.0031) and triglyceride (P=0.0476) compared with CONT (Dams and NP). Pregnancy did not accentuate the effects of FR on these outcomes. The second study compared the metabolic effects of intake of the fructose solution vs. distilled water on pregnant rats (Dams) and their female offspring (Offspring) when pregnant (Dam-FR, n=16; Dam-CONT, n=14) and female offspring when pregnant (Offspring-FR, n=10; Offspring-CONT, n=10). Fructose intake increased body weight (P=0.0003), plasma glucose, insulin and triglyceride concentrations (all P<0.0001) and % fat mass (P<0.0001) in Dams and Offspring. Offspring-FR had higher plasma triglyceride concentrations than Dams-FR (P=0.0099) and both CONT groups. Placenta from Dams-FR and Offspring-FR had increased mRNA expression of FABP1 (P=0.0004) but not other nutrient transporters (GLUT1 and SNAT2). Markers of angiogenesis (VEGF-A, P=0.0015; VEGFR-2, P=0.0014) were altered and CD31 expression was reduced (marker of endothelial cells; P=0.0129) with FR. Placentae and fetuses from Dams and Offspring given FR weighed less than those from CONT groups (P=0.0002 and P=0.0004, respectively). The third study compared the effect of intake of fructose (Dam-FR, n=14) vs. distilled water (Dam-CONT, n=12) on body weight and metabolic characteristics in two sequential pregnancies. Body weights were higher in the second than the first pregnancy (P<0.0001). Plasma glucose concentrations were higher in the second pregnancy at the mid-way point (P=0.0341) compared with the first pregnancy. Insulin concentrations were higher throughout the second vs. the first pregnancy (P=0.0182). Fructose intake did not exacerbate these effects. Overall, intake of a 10% fructose solution induces insulin resistance and hypertriglyceridemia in pregnant rats and the adverse effects of fructose intake during pregnancy were similar in the first and second pregnancy. Hypertriglyceridemia was more pronounced in pregnant Offspring consuming FR. This suggests that the effect of dietary programming on lipid metabolism occur in conjunction with a physiological challenge and points to the potential of dietary intake of fructose to adversely influence insulin resistance and lipid metabolism in mothers and their offspring when pregnant. Alterations in maternal metabolites and body composition were correlated with changes in placental development, particularly nutrient transporters, angiogenesis and vascular development. Overall changes in maternal metabolic profiles and placental development may be related to adverse health outcomes (such as hyperlipidemia) in the mother and offspring in later life.

  • Subjects / Keywords
  • Graduation date
    2017-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3BK1722Z
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Agricultural, Food, and Nutritional Science
  • Specialization
    • Nutrition and Metabolism
  • Supervisor / co-supervisor and their department(s)
    • Bell, Rhonda (Department of Agricultural, Food, and Nutritional Science)
  • Examining committee members and their departments
    • Dixon, Walter (Department of Agricultural Food and Nutritional Science)
    • Reimer, Raylene (Department of Biochemistry & Molecular Biology)
    • Hemmings, Denise (Department of Obstetric and Gynaecology and Medical Microbiology and Immunology)
    • Mazurak, Vera (Department of Agricultural, Food and Nutritional Science)