The vitamin D receptor is associated with inflammation in human skeletal muscle (LB423)

Abstract

Introduction: Emerging evidence suggests that vitamin D may play a direct role in inflammation mediated by skeletal muscle, possibly through the vitamin D receptor (VDR). Purpose: We examined two models, both a cross sectional and a longitudinal study of vitamin D3 supplementation to determine 1) the association between VDR protein expression and serum 25‐hydroxyvitaminD3 (25OHD) on intramuscular interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNFα) gene expression and protein concentration and 2) the effect of 16‐week supplementation with vitamin D3 on the association between VDR gene expression and IL‐6 and TNFα gene expression. Methods: Muscle biopsies of thirty older, mobility‐limited adults were obtained at baseline. A subset of 12 mobility limited women underwent 16 weeks of 4,000 IU vitamin D3 supplementation and biopsies were obtained at follow‐up. VDR, IL‐6 and TNFα gene expression gene expression and protein concentration were examined. Results: In cross‐sectional analysis intramuscular VDR protein concentration was positively associated with intramuscular IL‐6 gene expression (p=0.04), but serum 25OHD was not (p=0.8). Neither VDR protein or 25OHD was associated with intramuscular TNFα gene expression (p= 0.58; p=0.74). VDR protein concentration negatively predicted intramuscular IL‐6 protein concentration (p=0.03) but serum 25OHD did not (p=0.9). Neither VDR protein nor 25OHD was predictive of intramuscular TNFα protein (p=0.4; p=0.2). VDR gene expression was not associated with IL‐6 or TNFα gene expression or protein concentration (p>0.05). In the longitudinal study, VDR gene expression approached significant positive association with IL‐6 gene expression (p=0.06), but 25OHD did not (p=0.31) after vitamin D3 supplementation. Neither VDR nor 25OHD was associated with TNFα with vitamin D supplementation at baseline (p=0.89; p=0.84) or at follow‐up (p=0.09; p=0.32).Conclusion: This study provides support for the hypothesis that intramuscular vitamin D receptor, rather than serum 25‐hydroxyvitaminD3 status, affects intramuscular IL‐6 expression and concentration, but not TNFα, in human skeletal muscle.Grant Funding Source: Supported by USDA Agricultural Research Service, under agreements No. 58‐1950‐7‐707 (to BDH and LC) and No. 58‐1950‐0‐014 (to RAF); The Dairy Research Institute (R.A.F.), NHLBI pre‐doctoral training grant (T32HL69772 to RMP)