The immunomodulatory effect of dietary phosphatidylcholine within the context of obesity

  • Author / Creator
    Rusnak, Tianna
  • Obesity is a worldwide epidemic that is associated with immune dysfunction. In human
    and rodent models, obesity-induced immune dysfunction has been characterized by lower T cell
    proliferation and interleukin (IL)-2 production. While the mechanisms responsible for the
    observed reduction in T cell function is unclear, it has been suggested that lipotoxicity and
    increased intestinal permeability leading to bacterial translocation may play a role.
    Phosphatidylcholine (PC) is a lipid-soluble form of the essential nutrient choline that can be
    found in both animal and plant foods (i.e., eggs and soy). PC is an integral phospholipid in cell
    membranes and contributes to the hydrophobicity of the gastrointestinal mucosal layer. Our lab
    has shown that a diet containing 100% egg-PC enhances both peripheral and gut-associated T

    cell responses early in life when compared to a diet containing only free choline (FC), a water-
    soluble form of choline. Soy-derived PC has also been shown to support T cell response (albeit

    to a slightly lesser degree) and villi length. Further, we have shown that providing 100% egg-PC
    in a high-fat diet (HFD) improved T cell response when compared to a HFD containing only FC.
    However, no human diet contains choline solely in the form of PC. Therefore, the objective of
    this thesis was to determine the impact of feeding different doses and dietary forms of PC on
    immune function in a rodent model of obesity.

    In our first study, we examined the effect of different doses of PC in the context of a
    HFD. Male Wistar rats four weeks of age were randomized to consume one of six diets for 12
    weeks containing the same amount of total choline but differing in the forms of choline: 1-
    Control Low-fat (CLF, 20% fat, 100% free choline (FC)); 2- Control High-fat (CHF, 50% fat,
    100% FC); 3- 100% PC (100PC, 50% fat, 100% egg-PC); 4- 75% PC (75PC, 50% fat, 75% egg-

    PC+25% FC); 5- 50% PC (50PC, 50% fat, 50% egg-PC+50% FC); 6- 25% PC (25PC; 50% fat,
    25% egg-PC+75% FC). We observed that feeding the CHF diet increased intestinal permeability
    compared to the CLF diet, and doses of PC 50% of greater returned permeability to levels similar

    to that of the CLF diet. Feeding the CHF diet lowered splenocyte production of IL-1β, IL-2, IL-
    10, and tumor necrosis factor-alpha (TNF-α), and mesenteric lymph node (MLN) lymphocyte

    production of IL-2 compared to the CLF group. The 50PC diet most consistently significantly
    improved cytokine levels (IL-2, IL-10, TNF-α) compared to the CHF diet.

    In our second study, we examined the differential effect on immune function of egg- and
    soy-PC in the context of a HFD. Male Wistar rats were randomized to consume one of 4 diets
    for 12 weeks, all containing 1.5g of total choline/kg of diet but differing in choline forms: 1-
    CLF (100% FC); 2- CHF (100% FC); 3- High-fat Egg-derived PC (EPC, 100% Egg-PC); 4-
    High-fat Soy-derived PC (SPC, 100% Soy-PC). After T cell mitogen stimulation, the CHF-fed
    rats had a lower production of IL-2 compared to the CLF group which was normalized by

    feeding EPC and SPC. After T and antigen presenting cell (APC) mitogen stimulation, the CHF-
    fed rats had a lower production of IL-1B, IL-10 and TNF-α vs. the CLF group and feeding EPC

    normalized the production of IL-10 and TNF-α while SPC did not.

    Overall, we concluded that a dose of 50% of total choline derived from egg-PC can
    ameliorate HFD induced intestinal permeability and immune cell dysfunction. In addition, while
    both egg- and soy-PC have similar effects on intestinal permeability, egg-derived PC attenuates
    obesity-induced T cell dysfunction to a greater extent than soy derived PC.

  • Subjects / Keywords
  • Graduation date
    Fall 2023
  • 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.