• 1α;
  • 25-(OH)2-D3;
  • inflammation;
  • calcium;
  • reactive oxygen species;
  • cytokines


Objective: Obesity is associated with elevated oxidative stress and low-grade systemic inflammation. We have demonstrated recently that 1α,25-(OH)2-D3 promotes reactive oxygen species production in cultured adipocytes, whereas suppression of 1α,25-(OH)2-D3 by increasing dietary calcium down-regulates diet-induced oxidative stress in aP2-agouti transgenic mice. However, whether the anti-obesity effect of dietary calcium plays a role in regulation of obesity-associated inflammation is not clear.

Research Methods and Procedures: We investigated the role of dietary calcium in the regulation of inflammatory cytokine production in aP2-agouti transgenic mice fed low- and high-calcium obesigenic diets and in the modulation of cytokine production by 1α,25-(OH)2-D3 in cultured murine and human adipocytes.

Results: The high-calcium diet inhibited the expression of pro-inflammatory factors tumor necrosis factor α and interleukin (IL)-6 by 64% and 51%, respectively (p < 0.001), in visceral fat, stimulated the expression of the anti-inflammatory factors IL-15 and adiponectin by 52% (p = 0.001) and 54% (p = 0.025), respectively, in visceral fat, and induced a 2-fold increase in IL-15 expression in soleus muscle (p = 0.01) compared with litter mate controls on a low-calcium diet. 1α,25-(OH)2-D3 also markedly stimulated the expression of tumor necrosis factor α (p < 0.001) and IL-6 (p = 0.016) in differentiated 3T3-L1 adipocytes and increased IL-6 (p = 0.004) and IL-8 (p < 0.001) production in differentiated human adipocytes. These effects were blocked by calcium channel antagonism with nifedipine.

Discussion: These data demonstrate that 1α,25-(OH)2-D3 favors inflammatory cytokine expression and inhibits anti-inflammatory cytokine expression; accordingly, suppression of 1α,25-(OH)2-D3 by dietary calcium inhibits adipocyte-derived inflammation associated with obesity.