|Pojednic, Rachele - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Ceglia, Lisa - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Lichtenstein, Alice - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Dawson-hughes, Bess - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Fielding, Roger - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Endocrine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2014
Publication Date: 12/16/2014
Citation: Pojednic, R., Ceglia, L., Lichtenstein, A.H., Dawson-Hughes, B., Fielding, R.A. 2014. Vitamin D receptor protein is associated with interleukin-6 in human skeletal muscle. Endocrine. 49(2):512-520. https://doi.org/10.1007/s12020-014-0505-6.
Interpretive Summary: Vitamin D is expressed in human skeletal muscle and may play a role in muscular inflammation, possibly through the vitamin D receptor (VDR.) We can assess the presence of intramuscular inflammation via biomarkers, which are measurable substances in the body that are indicative of some phenomenon, such as inflammation. We conducted two studies to examine: 1) whether serum (blood) vitamin D and/or muscular VDR protein are associated with inflammation and 2) whether supplementation with vitamin D changes inflammation status. Muscle biopsies of older, mobility limited adults were analyzed. Baseline vitamin D in blood was not associated with inflammation. Baseline muscular VDR was positively associated with one biomarker but not the other. Neither biomarker was different between placebo- or vitamin D- supplemented adults after 16 weeks of supplementation. These data suggest that VDR is a better predictor than vitamin D (in blood) of inflammation and that vitamin D supplementation does not appear to affect biomarker expression after 16 weeks.
Technical Abstract: Vitamin D is associated with skeletal muscle physiology and function and may play a role in intramuscular inflammation, possibly via the vitamin D receptor (VDR). We conducted two studies to examine (1) whether serum 25-hydroxyvitamin D (25OHD) and/or intramuscular VDR protein concentrations are associated with intramuscular interleukin-6 (IL-6) and/or tumor necrosis factora (TNFa); and (2) whether 16-week supplementation with vitamin D3 alters intramuscular IL-6 and/or TNFalpha. Potential-related signaling pathways were also examined. Muscle biopsies of 30 older, mobility-limited adults were obtained at baseline. A subset of 12 women were supplemented with either 4,000 IU/day of vitamin D3 (N = 5) or placebo (N = 7), and biopsies were repeated at 16 weeks. Serum 25OHD was measured, and intramuscular VDR, IL-6, and TNFalpha gene expressions and protein concentrations were analyzed. Baseline serum 25OHD was not associated with intramuscular IL-6 or TNFalpha gene expression or protein concentration. Baseline intramuscular VDR protein concentration, adjusted for baseline serum 25OHD, was positively associated with intramuscular IL-6 gene expression (n = 28; p = 0.04), but negatively associated with intramuscular IL-6 protein (n = 18; p = 0.03). Neither intramuscular IL-6 nor TNFalpha gene expression was different between placebo (n = 7) or vitamin D3 supplementation groups (n = 5) after 16 weeks (p = 0.57, p = 0.11, respectively). These data suggest that VDR is a better predictor than serum 25OHD concentration of intramuscular IL-6 gene and protein expressions. A similar relationship was not observed for TNFalpha expression. Further, supplementation with 4,000 IU vitamin D3 per day does not appear to affect intramuscular IL-6 or TNFalpha gene expression after 16 weeks.