Dietary calcium and calcitriol regulate cytokine production in aP2‐agouti transgenic mice on high fat/high sucrose diets and in cultured murine and human adipocytes

Abstract

The interaction between reactive oxygen species (ROS) and inflammatory cytokines may contribute to the development of obesity associated pathologies. We previously demonstrated that calcitriol promotes adipocyte ROS production via regulation of Ca2+ signaling and metabolic uncoupling, while suppression of calcitriol by dietary calcium reduces ROS in aP2-agouti transgenic mice. Accordingly, we have investigated the effect of dietary calcium in regulating of inflammatory cytokine production in aP2-agouti transgenic mice and calcitriol modulation of cytokine production in cultured murine and human adipocytes. The high calcium diet markedly inhibited TNFα and IL-6 expression by 64% and 51% respectively (p<0.001) in visceral fat and stimulated IL-15 and adiponectin expression by 52% (p=0.001) and 54% (p=0.025). Consistent with this, calcitriol markedly stimulated pro-inflammatory cytokine expression in both 3T3-L1 adipocytes (TNFα and IL-6, p<0.02) and human adipocytes (IL-6 and IL-8, p<0.005). These effects were completely blocked by calcium channel antagonism with nifedipine, indicating that calctriol plays a direct role in regulating adipocyte cytokine expression via a Ca2+-dependent mechanism. Moreover, these results demonstrate that dietary calcium may inhibit obesity-induced inflammation in adipose tissue via suppression of calcitriol.