The Effects Of Perinatal Iron Deficiency On Brown Adipose Tissue And Whole-Body Energy Metabolism

  • Author / Creator
    Cherak, Stephana J
  • Developmental exposure to an adverse environment can lead to altered growth and developmental trajectories, thereby increasing susceptibility to chronic disease in later life. Iron deficiency (ID) is the most common nutritional disorder in the world, and pregnant women are the most susceptible subgroup. Perinatal ID (PID) has been shown to program offspring metabolic function, characterized by an increased propensity for fat accumulation in later life; however, the mechanisms underlying this metabolic dysfunction are unknown. Brown adipose tissue (BAT) is a highly active metabolic tissue that has the capacity to generate large quantities of heat. The capacity of BAT to burn calories as heat makes it an attractive therapeutic target for obesity. Conversely, dysfunctional or reduced thermogenic capacity of BAT may represent a factor that predisposes individuals to obesity. The purpose of these studies was to determine whether PID predisposes offspring to obesity by chronically altering the thermogenic capacity of BAT, and thus whole-body metabolism. Female Sprague Dawley rats were fed either an iron-restricted (3-10 mg/kg iron) or control diet (35 mg/kg iron) prior to and throughout gestation. At birth, dams were fed a normal rat chow, and offspring were fed a high-fat/high-sucrose diet at weaning (postnatal day [PD]21). At 4 wk of age, one male and female offspring from each litter were subjected to a chronic cold exposure protocol (4˚C, 12 h/day, 5 wk) to stimulate BAT, and one male and female littermate were maintained at room temperature (22˚C). Body composition was assessed using a whole-body composition analyzer. Metabolic parameters were analyzed in vivo via open-circuit indirect calorimetry, and maximal thermogenic capacity from BAT was assessed following pharmacological stimulation with the β3-adrenoceptor agonist, CL316,243. The expression levels of the thermogenic regulatory proteins were assessed in BAT. Adipose tissue morphology was assessed by light microscopy. Maternal iron restriction throughout pregnancy caused anemia and growth restriction in male and female offspring at birth. All offspring subsequently recovered in the neonatal period, such that hemoglobin (Hb) levels and body weight (BW) were no longer different between groups at PD21. Cold exposure increased intrascapular BAT (IBAT) mass, uncoupling protein-1 expression, and thermogenic capacity in all offspring, albeit these effects were diminished in the PID offspring. Whereas cold exposure had minimal effects on control offspring BW and body composition, cold exposure prevented BW and fat mass gain in male PID offspring, but not in female PID offspring. In summary, PID affects the quantity and thermogenic capacity of BAT in the offspring, albeit these differences are qualitatively different between males and females. Alterations in BAT physiology did not impair cold-induced loss of fat in offspring, suggesting alternative mechanisms may be implicated in chronic cold-stimulated weight loss. Nonetheless, the immense caloric burning capacity of BAT makes it an attractive target for therapeutic intervention to prevent obesity and metabolic dysfunction; however, albeit the extent to which such therapeutics are effective may depend on numerous factors, including perinatal health.

  • Subjects / Keywords
  • Graduation date
    2017-11:Fall 2017
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • 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
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Pharmacology
  • Supervisor / co-supervisor and their department(s)
    • Bourque, Stephane (Anesthesiology & Pain Medicine)
    • Gragasin, Ferrante (Anesthesiology & Pain Medicine)
  • Examining committee members and their departments
    • DeLorey, Darren (Physical Education and Recreation)
    • Hubbard, Basil (Pharmacology)
    • Yup, Jessica (Physiology)