Vitamin D Inhibits Adipokine Production and Inflammatory Signaling Through the Vitamin D Receptor in Human Adipocytes.

OBJECTIVE

The purpose of this study was to investigate the effects of vitamin D on adipokine expression and inflammation in human adipose tissues and adipocytes and evaluate the molecular mechanisms involved.

METHODS

Omental and abdominal subcutaneous human adipose tissues were treated with 1,25-dihydroxyvitamin D (1,25(OH) D ), and adipokine levels were measured. Vitamin D effects were measured with or without dexamethasone because glucocorticoids are known to affect vitamin D actions. Using RNA interference, we examined whether the vitamin D receptor (VDR) mediated vitamin D actions on adipokine expression and inflammatory signaling pathways in human adipocytes.

RESULTS

mRNA levels and secretion of leptin and IL-6 were suppressed by 1,25(OH) D in omental adipose tissues. Cotreatment with dexamethasone did not affect these inhibitory actions but partially blocked CYP24A1 induction. Similar results were observed in the subcutaneous depot. In addition, 1,25(OH) D suppressed leptin and IL-6 expression as well as nuclear factor-κB and extracellular signal-regulated kinase-1/2 phosphorylation in human adipocytes. Adipokine expression also was decreased by 25-hydroxyvitamin D (25(OH)D ), but not vitamin D . Knockdown of VDR increased the inflammatory signaling activity in the control condition and blocked the inhibitory effects of 1,25(OH) D on adipokine and inflammatory signaling pathways.

CONCLUSION

Vitamin D acts through VDR to inhibit inflammatory pathways and adipokine expression in human adipocytes. Increasing vitamin D status may ameliorate obesity-associated metabolic complications by decreasing adipose tissue inflammation.