Vitamin D and Adipose Tissue Inflammation

The objective of this project is to investigate whether vitamin D modulates chronic low-grade adipose tissue inflammation in overweight and obese, vitamin D deficient men and women. Obesity is associated with insulin resistance and an increased risk for type 2 diabetes mellitus. Numerous studies, mostly conducted in mouse models of obesity, strongly suggest that chronic low-grade inflammation of adipose and other tissues is the major mechanism by which increased adiposity is linked to insulin resistance. Adipose tissue inflammation may therefore be a promising therapeutic target to reduce insulin resistance and the risk of type 2 diabetes mellitus in obese individuals. Based on several lines of evidence, we hypothesize that vitamin D is an environmental factor that affects the course of the inflammatory response in most tissues of the body, including adipose tissue. In our previous studies, we found that circulating plasma concentrations of 25-hydroxy vitamin D (25-OH-D) and the primary degradation product 24,25-dihydroxy vitamin D (24,25-OH2-D) were significantly associated with adipose tissue expression of adiponectin and negatively with TNF-alpha, even when adjusted for body mass index. Because these previous studies were cross-sectional, it is critical to complete an intervention study in humans to determine whether the observed association of vitamin D levels and adipose tissue inflammation is causal. The objectives of this pilot study are therefore to collect relevant preliminary data, and to begin an exploration of the mechanisms underlying this association such as intestinal permeability. Increased intestinal permeability may contribute to chronic low-grade inflammation and signaling through the vitamin D receptor plays an important role in the maintenance of intestinal integrity. We will assess whether normalization of vitamin D status is associated with changes in intestinal permeability.