The role of dietary choline on the immune system through different life stages
Creators: Azarcoya Barrera, Jessy
Publisher: name: University of Alberta Library
Year: 2022

<p>Choline is an essential nutrient that can be found in the diet as water- (i.e., free choline (FC)) and lipid-soluble forms. Animal studies have demonstrated that choline is needed for optimal maternal immune function and immune system development in offspring. Moreover, the forms of choline modulate the development of the immune system differently, with diets high in phosphatidylcholine (PC; lipid-soluble form of choline) enhancing the development of the immune system to a greater extent than diets containing only FC in rodent. Despite evidence suggesting a greater impact of PC on immune responses, little is known about the role of sphingomyelin (SM), another lipid-soluble form, on immune system development. In addition, the benefits observed of dietary PC on immune function are consistently accompanied by an increased T cell proliferation as measured by higher interleukin (IL)-2 production. Obesity is characterized by the presence of immune dysfunction in both rodents and humans where a lower IL-2 production upon T cell stimulation is typically observed. To date, it is unknown whether dietary choline, especially the lipid-soluble forms, would counteract the obesity-related immune dysfunction observed in the state of obesity. Therefore, the objective of this thesis was to determine the impact of feeding different forms of choline on the immune system through different life stages (i.e., early in life and obesity).<br>
    In a series of experiments, we aimed to determine the impact of feeding diets high in SM and/or PC on immune responses of lactating dams and local and peripheral immune systems development in offspring. Dams were fed one of three experimental diets all containing the same amount of total choline but differing in the form of choline: 1) a control diet containing only FC (water-soluble form); 2) a 50%PC diet (50% PC, 25% GPC and 25% FC); 3) a diet high in SM and PC (SMPC, 34-36% each). We observed that the forms of choline in the maternal diet were able to modulate the proportion of choline forms in breastmilk. Moreover, diets containing a high proportion of choline in the form of SM, improved T cells response in lactating dams by increasing ex vivo IL-2, TNF-α, and IFN-γ production by splenocytes. Meanwhile, growth was improved in offspring from the SMPC group. In addition, both diets containing a high proportion of lipid-soluble forms (at least 50%) improve the maturation of peripheral immune responses in suckled pups by increasing the production by splenocytes of TNF-α, and IFN-γ following T cells mitogen stimulation. In weaned pups (10 weeks of age), peripheral immune responses were enhanced by both diets high in lipid-soluble forms of choline. There was a higher production of IL-2 by splenocytes along with IFN-γ after T cell mitogen stimulation. Moreover, the lipid-soluble forms of choline positively modulated T cell responses in the gut by increasing IL-2, TNF-α, and IFN-γ production in mesenteric lymph nodes (MLN) and the proportion of B cells in Peyer’s patches. In addition, upon dietary antigen stimulation, there was a lower production of IL-2, TNF-α, and IL-6 and higher IL-10 production by immune cells from both spleen and MLN suggesting that the lipid-soluble forms of choline could potentially favor the development of oral tolerance.<br>
    In a parallel study, we examined the effect of dietary PC in the context of a high-fat diet (HFD) feeding. Male Wistar rats were randomized to consumed one of three experimental diets: a control low-fat diet (FC only); a control HFD (FC only) and a HFD with PC as the main source of dietary choline. We observed that when fed the control HFD, Wistar rats had a lower ex vivo IL-2 and TNF-α production by splenocytes when compared to the control low-fat diet. When adding PC to a HFD these changes were no longer observed.<br>
    Overall, we concluded that the lipid-soluble forms of choline provide more benefits for the development of both local and peripheral immune responses and the establishment of oral tolerance early in life. In addition, these results were also translated to a different model (HFD feeding) where we observed that the lipid-soluble forms (PC) can attenuate to some extent the obesity-related immune dysfunction.</p>