1:00 pm - 2:00 pm
A graduate exam seminar is a presentation of the student’s final research project for their degree.
This is an ALES PhD Final Exam Seminar by Jessy Azarcoya Barrera. This seminar is open to the general public to attend.
Meeting ID: 980 0133 8889 | Passcode: 387599
Thesis Topic: The role of dietary choline on the immune system through different life stages
PhD with Drs. Rene Jacobs and Caroline Richard.
Choline is an essential nutrient that can be found in the diet as water- (i.e., free choline (FC)) and lipid-soluble (i.e., phosphatidylcholine (PC) and sphingomyelin (SM)) forms. Previous studies have demonstrated that choline is needed for optimal maternal immune function and the immune system development in offspring with the most benefits being observed when choline was provided as PC in rodents. Yet, this is not representative of the choline forms distribution in a human diet. Despite evidence suggesting a greater impact of PC on immune responses when compared to FC, little is known about the role of SM, another important dietary form of choline, on the immune system. In rodents, feeding dietary PC has been shown to enhance T cell function by increasing the production of Th1 cytokines (i.e. IFN-γ and TNF-α) and IL-2 (a proliferation marker) upon stimulation. In both rodents and humans, obesity has been associated with impaired T cell function characterized by a lower IL-2 and Th1 cytokines production upon T cell stimulation. To date, it is unknown whether dietary choline, especially the lipid-soluble forms, could counteract the obesity-related immune dysfunction. Therefore, the objective of this thesis was to determine the impact of feeding different forms of choline on the immune system in different life stages (i.e. lactation period, postnatal period and obesity in adulthood).
A series of experiments were conducted 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 their offspring. We observed that the forms of choline in the maternal diet were able to modulate the proportion of choline forms in breastmilk during the lactation period. Feeding lactating dams a diet high in SM and PC (34-36% each) improved T cell response by increasing the ex vivo production of IL-2, TNF-α, and IFN-γ by splenocytes. In addition, when dams were fed diets containing a high proportion of lipid-soluble forms (at least 50%) T cell responses were enhanced in both suckled and weaned pups where a higher production of IL-2 TNF-α, and IFN-γ by splenocytes was observed. Similarly, in mesenteric lymph nodes (MLN) of weaned pups, the lipid-soluble forms of choline positively modulated T cell responses in the gut by increasing IL-2, TNF-α, and IFN-γ production. Moreover, upon dietary antigen stimulation, there was a lower production of IL-2, TNF-α, and IL-6 and a higher production of IL-10 by immune cells from both the spleen and MLN in weaned pups, suggesting that the lipid-soluble forms of choline could potentially favor the development of oral tolerance (i.e. lower the risk of allergies).
Finally, the effect of dietary PC on the immune system in obesity was assessed using a Wistar rat model fed a high-fat diet (HFD). We demonstrated that feeding a HFD in male rats led to an impaired T cell function by lowering the ex vivo production of IL-2 and TNF-α by splenocytes when compared to the control low-fat diet (CLF). Moreover, we showed that feeding PC as part of a HFD normalized the production of these cytokines in that they were no longer different from the CLF group.
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.