Braga Tibaes Jenneffer Rayane, Azarcoya-Barrera Jessy, Wollin Bethany, Veida-Silva Hellen, Makarowski Alexander, Vine Donna, Tsai Sue, Jacobs René, Richard Caroline
Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Metabolic and Cardiovascular Diseases Laboratory, University of Alberta, Edmonton, Alberta, Canada.
J Nutr. 2022 May 5;152(5):1347-1357. doi: 10.1093/jn/nxac024.
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.
The objective was to determine sex differences on immune function in response to an HFD compared with a control low-fat diet (LFD) in Wistar rats.
At 5 wk of age, male and female Wistar rats were randomly assigned to 1 of 2 diets for 9 wk: 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 wk of age, rats were killed 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-factor ANOVA was used to assess the main effect of sex, diet, and their interaction.
Males gained more weight than females (410 ± 46 vs. 219 ± 45 g), independently of diet (P-sex < 0.01). The 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 phorbol 12-myristate 13-acetate plus ionomycin (PMA+I), as well as a higher T-helper (Th) 1:Th2 balance compared with HFD-fed males (all P < 0.05). Males fed the HFD had significantly lower production of IL-2 upon stimulation compared with all other groups.
Female Wistar rats developed a milder obesity phenotype and maintained enhanced cytokine production compared with 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.
肥胖期间免疫功能会发生改变。此外，不同物种的雄性和雌性对多种疾病表现出不同的易感性。然而，关于高脂饮食（HFD）与性别在免疫功能方面的相互作用，人们了解得较少。
目的是确定与对照低脂饮食（LFD）相比，高脂饮食对Wistar大鼠免疫功能的性别差异。
5周龄时，将雄性和雌性Wistar大鼠随机分为两种饮食之一，持续9周：自由采食对照低脂饮食（20千卡%脂肪、53千卡%碳水化合物和27千卡%蛋白质）或高脂饮食（50千卡%脂肪、23千卡%碳水化合物和27千卡%蛋白质）。13周龄时，处死大鼠并分离脾细胞。通过流式细胞术确定免疫细胞亚群。通过测量用丝裂原刺激后体外细胞因子的产生来确定免疫细胞功能。采用双因素方差分析评估性别、饮食及其相互作用的主要影响。
无论饮食如何，雄性比雌性体重增加更多（410±46对219±45克）（P性别<0.01）。高脂饮食导致白细胞介素-2（IL-2）产生降低，同时白细胞介素-10（IL-10）产生增加（两者P饮食≤0.05），与性别无关。与高脂饮食喂养的雄性相比，高脂饮食喂养的雌性在用佛波醇12-肉豆蔻酸酯13-乙酸酯加离子霉素（PMA+I）刺激后细胞因子（IL-2和IL-6）产生增加，以及辅助性T细胞（Th）1:Th2平衡更高（所有P<0.05）。与所有其他组相比，高脂饮食喂养的雄性在刺激后IL-2产生显著降低。
与高脂饮食喂养的雄性相比，雌性Wistar大鼠肥胖表型较轻，细胞因子产生维持增强。在高脂喂养情况下，性别差异调节免疫功能，在建立个性化健康相关建议的研究设计中应予以考虑。
