Investigations of the Anti-inflammatory Effects of Vitamin D in Adipose Tissue: Results from an In Vitro Study and a Randomized Controlled Trial

Inflammation is a key feature of obesity and type 2 diabetes. The active vitamin D metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], modulates the inflammation in vitro. We studied whether inflammation in adipose tissue (AT) cultures could be reduced by incubation with 1,25(OH)(2)D in vitro, or by oral treatment with vitamin D in vivo in obese subjects with low plasma levels of 25-hydroxyvitamin D. Samples of subcutaneous AT were stimulated with IL-1 beta to induce inflammation. In the in vitro study, samples were concomitantly incubated with or without 1,25(OH)(2)D, and analyzed for mRNA and protein levels of inflammatory markers IL-6, IL-8, and MCP-1. In the in vivo study, samples of subcutaneous AT from obese subjects obtained before and after treatment with 7000 IU of vitamin D daily or placebo in a randomized controlled trial were stimulated with IL-1 beta. The samples were analyzed for AT gene expression and compared with plasma markers of inflammation. In the in vitro study, concomitant incubation with 1,25(OH)(2)D reduced mRNA levels of MCP-1 by 45 % (p = 0.01), of IL-6 by 32 % (p = 0.002), and of IL-8 by 34 % (p = 0.03), and reduced secretion of IL-8 protein by 18 % (p = 0.005). In vivo treatment with vitamin D did not reduce AT expression or circulating levels of MCP-1, IL-6, or IL-8. 1,25(OH)(2)D has significant anti-inflammatory effects in AT in vitro. However, a similar reduction in AT and systemic inflammation cannot be obtained by oral treatment with vitamin D in obese subjects.