Park CY, et al. J Lipid Atheroscler. 2021 May;10(2):130-144. https://doi.org/10.12997/jla.2021.10.2.130

Numerous studies have established associations between vitamin D and diabetes. The vitamin D receptor is widely distributed throughout the human body, including in pancreatic beta cells (β-cells), hepatocytes, and immune cells. Therefore, vitamin D’s effect on the risk, progression, or complications of diabetes may be mediated through various mechanisms. These include the regulation of insulin secretion or sensitivity and modulation of β-cell function and its immunomodulatory and anti-inflammatory effects. This review extensively explores the relationship between vitamin D status and diabetes, as well as the preventive or therapeutic effects of vitamin D supplementation on diabetes from human studies. Additionally, it examines in detail the impact of vitamin D on immune and inflammatory responses in the diabetic milieux and β-cell function to better understand the underlying mechanisms through which vitamin D influences diabetes.

Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iκba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.

Obesity has been reported to be associated with iron deficiency. However, few studies have investigated iron status in low adiposity. To investigate whether body adiposity was associated with altered hepatic iron status, we compared liver iron levels and markers involved in inflammation and iron absorption in obese, control, and mildly calorie restricted mice. Seven week old C57BL/6 mice were fed control (10% kcal fat, Control) or high fat (60% kcal fat, HFD) diets, or reduced amount of control diet to achieve 15% calorie restriction (CR) for 16 weeks. Hepatic non-heme iron content and ferritin protein level, and hematocrit and hemoglobin levels were determined to assess iron status. Hepatic expression of Mcp-1 and Tnf-α were measured as hepatic inflammatory markers. Hepatic hepcidin (Hamp) and Bmp6, and duodenal Dmt1, Dcyt1b, hephaestin (Heph) and ferroportin mRNA levels were measured as factors involved in regulation of iron absorption. Hepatic non-heme iron and ferritin protein levels were significantly higher in the CR group compared with the Control group, and significantly lower in the HFD group. These two iron status markers showed significantly negative correlations with the amount of white adipose tissue (r = -0.689 for hepatic non-heme iron and r = -0.740 for ferritin). Hepatic Mcp-1 and Tnf-α mRNA levels were significantly lower in the CR compared with the HFD (74 and 47% lower) and showed significantly negative correlations with hepatic non-heme iron levels (Mcp-1: r = -0.557, P < 0.05; Tnf-α: r = -0.464, P < 0.05). Hepatic Hamp mRNA levels were lower in the HFD and higher in the CR groups compared with the Control group, which could be a response to maintain iron homeostasis. Duodenal Dcyt1b mRNA levels were higher in the CR group compared with the HFD group and duodenal Heph mRNA levels were higher in the CR group than the Control group. We showed that body adiposity was inversely correlated with liver iron status. Low inflammation levels in hepatic milieu and enhanced expression of duodenal oxidoreductases induced by calorie restriction could have contributed to higher iron status.