1:00 pm - 2:00 pm
4-113 Li Ka Shing Centre (LKS), University of Alberta, Edmonton AB
Event details: A graduate exam seminar is a presentation of the student’s final research project for their degree.
This is an ALES MSc Final Exam Seminar by Tianna Rusnak. This seminar is open to the general public to attend.
MSc with Dr. Caroline Richard.
Thesis Topic: The immunomodulatory effect of dietary phosphatidylcholine within the context of obesity
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.