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Effects of in vitro vitamin D treatment on function of T cells and autophagy mechanisms in high-fat diet-induced obese mice

  • Kang, Min Su (Department of Food and Nutrition, College of Human Ecology, Seoul National University) ;
  • Park, Chan Yoon (Department of Food & Nutrition, College of Health Science, The University of Suwon) ;
  • Lee, Ga Young (Department of Food and Nutrition, College of Human Ecology, Seoul National University) ;
  • Cho, Da Hye (Department of Food and Nutrition, College of Human Ecology, Seoul National University) ;
  • Kim, So Jeong (Department of Food and Nutrition, College of Human Ecology, Seoul National University) ;
  • Han, Sung Nim (Department of Food and Nutrition, College of Human Ecology, Seoul National University)
  • Received : 2021.02.09
  • Accepted : 2021.05.04
  • Published : 2021.12.01

Abstract

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 in vitro 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)2D3 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. RESULTS: 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)2D3 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. CONCLUSIONS: 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.

Keywords

Acknowledgement

This research was supported by grants from National Research Foundation (NRF) of Korea (NRF-2018R1D1A1B07049178).

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