Calcitriol and the Renin Angiotensin System, and Adipose Tissue Inflammation

Adipose tissue is well recognized as an endocrine organ and a source of proinflammatory molecules ¹. We recently demonstrated calcitriol stimulates adipocte reactive oxygen species (ROS) production and inflammatory stress (IS), while dietary calcium suppression of calcitriol exerted the opposite effect. These effects are mediated, in part, by calcitriol modulation of intracellular calcium (Ca²⁺) signaling and mitochondrial potential. However, adipocytes contain a functional RAS, and angiotensin II (ANGII) modulates ROS and IS. Accordingly, we investigated the role of ANGII in mediating calcitriol effects. Calcitriol (1 nM) stimulated NOX4 expression and ROS production in 3T3-L1 adipocytes by 67% (p<0.01), while these effects were reversed by ACE inhibition (enalipril) or antagonism of either ANGII type 1 receptor (AT1R) or ANGII type 2 receptor (AT2R), antagonism. Similarly, ANG (0-.1-1.0 nM) stimulated NOX4 expression (p<0.03) and this effect was reversed by AT1R or AT2R antagonism. Calcitriol and ANGII both suppressed adiponectin expression (p<0.04) and increased IL6 and MCP-1 expression ~2 fold (p<0.03), and these effects were reversed with enalapril or AT2R, but not AT1R, antagonism. These data demonstrate that calcitriol modulation of adipocyte ROS production and IS is modulated, in part, by the adipocyte RAS.