The immunomodulatory effect of dietary phosphatidylcholine within the context of obesity
Creators: Rusnak, Tianna
Publisher: name: University of Alberta Library
Year: 2023

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

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

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

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

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

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

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

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

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

<p>normalized the production of IL-10 and TNF-α while SPC did not.</p>

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