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-3 (1,25(OH)(2)D-3), 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)(2)D-3 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)(2)D-3 suppressed leptin and IL-6 expression as well as nuclear factor-kappa B and extracellular signal-regulated kinase-1/2 phosphorylation in human adipocytes. Adipokine expression also was decreased by 25-hydroxyvitamin D-3 (25(OH)D-3), but not vitamin D-3. Knockdown of VDR increased the inflammatory signaling activity in the control condition and blocked the inhibitory effects of 1,25(OH)(2)D-3 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.

Automated summary

Vitamin D inhibits inflammatory pathways and adipokine expression in human adipocytes through VDR. Improving vitamin D status may alleviate obesity-related metabolic complications by reducing adipose tissue inflammation.