Background : Immune function is altered during obesity. Moreover, males and females across different species demonstrate distinct susceptibility to several diseases. However, less is known regarding the interplay between high-fat diet (HFD) and sex in the context of immune function. Objective The objective was to determine sex differences on immune function in response to a HFD compared to a control low-fat diet (LFD) in Wistar rats. Methods At 5 weeks of age, male and female Wistar rats were randomized to one of two diets for 9 weeks: ad libitum control LFD (20% kcal% fat, 53 kcal% carbohydrate, and 27 kcal% protein) or HFD (50% kcal% fat, 23 kcal% carbohydrate, and 27 kcal% protein). At 13 weeks of age, rats were euthanized and splenocytes were isolated. Immune cell subsets were determined by flow cytometry. Immune cell function was determined by measuring the ex vivo cytokine production following stimulation with mitogens. Two-way ANOVA was used to assess the main effect of sex, diet, and their interaction. Results : Males gained more weight compared to females (410 ± 46 vs 219 ± 45 g), independently of diet (P-sex <0.01). HFD led to a lower production of IL-2 while increasing the production of IL-10 (both P-diet ≤ 0.05), independently of sex. HFD-fed females had increased production of cytokines (IL-2 and IL-6) after stimulation with PMA+I, as well as a higher Th1:Th2 balance compared to HFD-fed males (all P <0.05). Males fed the HFD had significantly lower production of IL-2 upon stimulation compared to all other groups. Conclusion : Female Wistar rats developed a milder obesity phenotype and maintained enhanced cytokine production compared to males fed the HFD. Sex differences modulate immune function in the context of high-fat feeding and it should be considered in research design to establish personalized health-related recommendations.

Obesity is associated with immune dysfunction including an impaired T-cell function characterized by a lower IL-2 (proliferation marker) production after stimulation. Phosphatidylcholine (PC), a form of choline mostly found in eggs, has been shown to beneficially modulate T-cell responses during the lactation period by increasing the production of IL-2. To determine the impact of egg-PC as part of a high-fat diet on immune function we randomly fed male Wistar rats one of three diets containing the same amount of total choline but differing in the form of choline: 1—Control low fat [CLF, 10% wt/wt fat, 100% free choline (FC)]; 2— Control high-fat (CHF, 25% wt/wt fat, 100% FC); 3— PC high-fat (PCHF, 25% wt/wt, 100% PC). After 9 weeks of feeding, rats were euthanized. Cell phenotypes and ex vivo cytokine production by splenocytes stimulated with phorbol 12-myristate 13-acetate plus ionomycin (PMA+I), lipopolysaccharide (LPS) and pokeweed (PWM) were measured by flow cytometry and ELISA, respectively. Rats fed the PCHF diet had a lower proportion of CD3+ cells when compared to both the CLF and the CHF. Following PMA+I stimulation, splenocytes from the CHF group produced less IL-2 and TNF-α compared to CLF and PCHF groups. No significant differences in cytokine production were found among groups after LPS and PWM stimulation. Our results show that feeding a high-fat diet impairs T-cell responses, as measured by ex vivo cytokine production, which can be attenuated by providing egg-PC.

Objectives Obesity and insulin resistance (IR) are associated with systemic inflammation, lower immune function, and a higher risk of infection. We previously reported that individuals with obesity and type 2 diabetes have an impaired T cell response (i.e., lower IL-2 production, a marker of proliferation) upon T cell stimulation despite having more activated T cells compared to normoglycemic (NG) individuals with obesity. It remains unclear if the immune dysfunction is caused by adiposity, hyperglycemia and/or dietary patterns. The aim of this study was to investigate the effect of consuming an isocaloric North American-type diet on the IL-2 receptor (CD25) expression and cardiometabolic risk factors in lean, obese-NG, and obese-IR individuals. Methods This is a three parallel-arm trial in controlled feeding conditions being conducted at the Human Nutrition Research Unit, at the University of Alberta. Three groups of adults: Lean-NG (n = 7), Obese-NG (n = 8), and Obese-IR (n = 9) consumed an isocaloric standardized diet containing 35% fat, 48% carbohydrate, and 17% protein for 4 weeks. All meals were provided to participants. Blood samples were collected in the fasting state before and after the intervention and cardiometabolic risk factors were measured. Peripheral blood mononuclear cells (PBMCs) were isolated and the proportion of total immune cells expressing CD25 was determined by flow cytometry. Results At baseline and post-intervention, Obese-IR had higher levels of glucose, insulin, and HOMA-IR and lower levels of HDL-C compared to both Lean-NG and Obese-NG groups (P < 0.05). At baseline, the proportion of PBMCs expressing CD25 tended to be lower in the Lean-NG (17.6 ± 2.7) compared to both Obese-NG (23.3 ± 4.8) and Obese-IR (23.2 ± 4.8) (P = 0.08). Post-intervention, the expression of CD25 was reduced in Lean-NG and Obese-IR groups (P < 0.01) but similar trends were still observed among all groups (P = 0.07). Conclusions Our preliminary data suggest that obesity, independent of IR, is associated with greater activation of immune cells and consuming a North American-type diet lowers the expression of the IL-2 receptor in individuals with and without obesity. Therefore, both excess adiposity and dietary pattern appear to modulate the function of immune cells in obesity. Funding Sources Canadian Institutes of Health Research.

Objectives Studies have suggested that high-fat (HF) diets are associated with immune dysfunction, which results in a lower production of IL-2 and a lower proportion of helper T cells. Providing a diet containing 100% phosphatidylcholine (PC), a form of choline mainly found in eggs, has been shown to increase IL-2 production early in life. However, this is of no relevance for human consumption since no human diet will contain 100% PC. Therefore, the objective of this study was to determine the dose effect of egg-PC added to a high fat diet compared to a control high fat and low fat diets on T cell function in male Wistar rats. Methods At four weeks of age, male Wistar rats were randomized to consume one of 6 diets: 1- Control low fat (CLF, 10%wt/wt fat, 100% free choline (FC), n = 10); 2- Control high fat (CHF, 25% wt/wt fat, 100% FC, n = 10); 3- 100% PCHF (100PCHF, 25% wt/wt fat, 100% PC, n = 10); 4- 75% PCHF (75PCHF, 25% wt/wt fat, 75% PC, 25% FC, n = 10); 5- 50% PCHF (50PCHF, 25% wt/wt fat, 50% PC, 50% FC, n = 10); 6- 25% PCHF (25PCHF; 25% wt/wt fat, 25% PC, 75% FC, n = 10). Fatty acid composition was closely matched in all of the diets. Anthropometric data was collected through the duration of the study (12 weeks). At the end of the study, splenocytes phenotypes were measured by flow cytometry. Results From week 1 to week 10 there was no difference in body weight between the diets. Starting from week 2 the CLF group had a higher food intake compared to the other groups. The 50PCHF diet had a higher proportion of helper T cells (CD4+) compared to the CLF and CHF diets. In addition, 50PCHF had a higher proportion of helper T cells expressing IL-2 receptors (CD4+CD25+) compared to 25PCHF (P < 0.05). 50PCHF also had a higher proportion of T cells expressing a memory marker (CD3+CD27+) compared with all HF diets (all P < 0.05) but not the CLF diet. Conclusions Our results suggest that a diet providing 50% of total choline in the form of egg-PC normalizes the proportion of T cells expressing CD27 in the context of a HF diet which may lead to a better immune response if a second exposure to a pathogen occurs. Whether the higher proportion of helper T cells expressing the IL-2 receptor in the 50PCHF group is associated with better T cell response upon challenge remains to be investigated. Funding Sources Egg farmers of Canada, NSERC.