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.

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ABSTRACT Background Buttermilk contains a mixture of choline forms; it is high in phosphatidylcholine (PC) and sphingomyelin (SM), which could have an impact on immune system development and function. Objectives We aimed to determine the effect of feeding buttermilk-derived choline forms during pregnancy and lactation on maternal immune function. Methods Sprague Dawley dams (n = 8 per diet) were randomly assigned midway through pregnancy (10 d of gestation) to 1 of 3 experimental diets, containing 1.7 g/kg choline: control [100% free choline (FC)]; buttermilk [37% PC, 34% SM, 17% glycerophosphocholine (GPC), 7% FC, 5% phosphocholine]; or placebo (50% PC, 25% FC, 25% GPC). Dams consumed the same diet until the end of the lactation period (21 d after parturition). Cell phenotypes and cytokine production by mitogen-stimulated splenocytes were measured and compared using 1-factor ANOVA test in order to asses the effect of diet on immune fuction of lactating dams (main outcome). Results After ConA stimulation, splenocytes from dams in the buttermilk group produced more IL-2 (30%), TNF-α (30%), and IFN-γ (42%) compared with both the placebo and control diets. Placebo-fed dams had a higher proportion of CD8+ cells expressing CD152+ (22%) in spleen, and splenocytes from dams that were fed the buttermilk and the placebo diets produced about 50% and 53% more IL-10 after LPS and OVA stimulation, respectively, compared with the control group. Conclusions Feeding buttermilk-derived choline forms during pregnancy and lactation had a beneficial impact on the immune system of Sprague Dawley rat dams, especially on T-cell function.

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.