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
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.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Tumor Necrosis Factor alpha expression in adipose tissue
Total RNA will be extracted from whole adipose tissue. TNF alpha mRNA will be quantified using PCR, and normalized using a normalization factor based on three housekeeping genes. We will compute the change in adipose tissue TNF alpha mRNA level between baseline and the 6 month visit.
Change from baseline to the 6 month visit
Mario Kratz, Ph.D.
Fred Hutchinson Cancer Research Center
United States: Institutional Review Board
UW NORC P&F KRATZ
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|