Kang Min Su, Park Chan Yoon, Lee Ga Young, Cho Da Hye, Kim So Jeong, Han Sung Nim
Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea.
Department of Food & Nutrition, College of Health Science, The University of Suwon, Hwaseong 18323, Korea.
Nutr Res Pract. 2021 Dec;15(6):673-685. doi: 10.4162/nrp.2021.15.6.673. Epub 2021 May 14.
BACKGROUND/OBJECTIVES: Obesity is associated with the impaired regulation of T cells characterized by increased numbers of Th1 and Th17 cells and the dysregulation of vitamin D metabolism. Both obesity and vitamin D have been reported to affect autophagy; however, a limited number of studies have investigated the effects of vitamin D on T cell autophagy in obese mice. Therefore, we aimed to determine whether treatment with vitamin D affects the proliferation, function, and autophagy of T cells from obese and control mice.
MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed control or high-fat diets (10% or 45% kcal fat: CON or HFDs, respectively) for 12 weeks. Purified T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies and cultured with either 10 nM 1,25(OH)D or 0.1% ethanol (vehicle control). The proliferative response; expression of CD25, Foxp3, RORγt, and autophagy-related proteins (LC3A/B, SQSTM1/P62, BECLIN-1, ATG12); and the production of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and IL-10 by T cells were measured.
Compared with the CON group, T cell proliferation tended to be lower, and the production of IFN-γ was higher in the HFD group. IL-17A production was reduced by 1,25(OH)2D treatment in both groups. The LC3 II/I ratio was higher in the HFD group than the CON group, but P62 did not differ. We observed no effect of vitamin D treatment on T cell autophagy.
Our findings suggest that diet-induced obesity may impair the function and inhibit autophagy of T cells, possibly leading to the dysregulation of T cell homeostasis, which may be behind the aggravation of inflammation commonly observed in obesity.
背景/目的：肥胖与T细胞调节受损有关，其特征为Th1和Th17细胞数量增加以及维生素D代谢失调。肥胖和维生素D均已被报道会影响自噬；然而，仅有少数研究探讨了维生素D对肥胖小鼠T细胞自噬的影响。因此，我们旨在确定维生素D治疗是否会影响肥胖小鼠和对照小鼠T细胞的增殖、功能及自噬。
材料/方法：给5周龄雄性C57BL/6小鼠分别喂食对照饮食或高脂饮食（分别含10%或45%千卡脂肪：分别为CON或HFDs）12周。用抗CD3和抗CD28单克隆抗体刺激纯化的T细胞，并用10 nM 1,25(OH)D或0.1%乙醇（溶剂对照）进行培养。检测T细胞的增殖反应；CD25、Foxp3、RORγt和自噬相关蛋白（LC3A/B、SQSTM1/P62、BECLIN-1、ATG12）的表达；以及T细胞产生干扰素（IFN）-γ、白细胞介素（IL）-4、IL-17A和IL-10的情况。
与CON组相比，HFD组T细胞增殖倾向于更低，且IFN-γ产生更高。两组中1,25(OH)2D治疗均使IL-17A产生减少。HFD组的LC3 II/I比率高于CON组，但P62无差异。我们观察到维生素D治疗对T细胞自噬无影响。
我们的研究结果表明，饮食诱导的肥胖可能损害T细胞功能并抑制其自噬，可能导致T细胞稳态失调，这可能是肥胖中常见炎症加剧的原因。
