Maternal vitamin D deficiency increases the risk of obesity in male offspring mice by affecting the immune response

Objectives: Recently, many epidemiologic and animal studies have indicated that obesity has its origin in early stages of life, including the inappropriate balance of some nutrients. So the objectives of this study were to determine the risk of obesity in male offspring mice as a consequence of maternal vitamin D (VD) deficiency mediating the disordered immune response. Methods: C57BL/6J female mice 4 wk old were fed VD-deficient or normal reproductive diets during pregnancy and lactation. Their male offspring were given control and high-fat diets for 16 wk after weaning and then weighed and euthanized. The serum was collected for biochemical analyses. Epididymal (eWAT) and inguinal white adipose tissue (iWAT) were excised for histologic examination, immunohistochemistry, gene expression of inflammatory factors, and determination by flow cytometry of the proportions of immune cells. Results: Insufficient maternal VD intake exacerbated the development of obesity in male offspring mice that were both obese and non-obese, as evidenced by larger adipose cells and abnormal glucose and lipid metabolisms. Also, the expressions of proinflammatory cytokines were increased and that of anti-inflammatory cytokines was decreased in eWAT and/or iWAT in the maternal VD-deficient group, accompanied by higher levels of tumor necrosis factor-alpha and/or interferon-gamma and lower levels of interleukin-4 and interleukin-10. Insufficient maternal VD intake was also observed to induce a shift in the profiles of immune cells in the eWAT and/or iWAT of male offspring that were both obese and non-obese, resulting in increased percentages of M1 macrophages, adipose tissue dendritic cells, and CD4(+) and CD8(+) T cells but a significant decrease in the percentages of M2 macrophages. All these changes in the immune cell profile were more obvious in the eWAT than those in the iWAT. Conclusions: Maternal VD deficiency might promote the development of obesity in male offspring mice partly by modulating the immune cell populations and causing a polarization in the adipose depots. (C) 2021 Elsevier Inc. All rights reserved.