Objective: We have previously demonstrated that 1 alpha, 25( OH)(2)D-3 promotes adipocyte reactive oxygen species ( ROS) production. We have now evaluated whether decreasing 1a, 25( OH) 2D3 levels by increasing dietary calcium will decrease oxidative stress in vivo. Methods: We fed low-calcium ( 0.4% Ca) and high-calcium ( 1.2% Ca from CaCO3) obesity-promoting ( high sucrose/high fat) diets to aP2-agouti transgenic mice and assessed regulation of ROS production in adipose tissue and skeletal muscle. Results: Mice on the high-calcium diet gained 50% of the body weight ( P = 0.04) and fat ( P < 0.001) as mice on the low-calcium diet ( 0.4% Ca). The high-calcium diet significantly reduced adipose intracellular ROS production by 64 and 18% ( P < 0.001) and inhibited adipose tissue nicotinamide adenine dinucleotide phosphate oxidase expression by 49% ( P = 0.012) and 63% ( P = 0.05) in visceral and subcutaneous adipose tissue, respectively. Adipocyte intracellular calcium ([ Ca2+](i)) levels were suppressed in mice on the high-calcium diet by 73 - 80% ( P < 0.001). The high-calcium diet also induced 367 and 191% increases in adipose mitochondrial uncoupling protein 2 ( UCP2) expression ( P < 0.001) in visceral and subcutaneous adipose tissue, respectively. The pattern of UCP3 expression and indices of ROS production in skeletal muscle were consistent with those in adipose tissue. The high-calcium diet also suppressed 11 beta-hydroxysteroid dehydrogenase ( 11 beta-HSD) expression in visceral adipose tissue by 39% ( P = 0.034). 11 beta-HSD expression was markedly higher in visceral vs subcutaneous adipose tissue in mice on the low-calcium diet ( P = 0.034), whereas no difference was observed between the fat depots in mice on the high-calcium diet. Conclusion: These data support a potential role for dietary calcium in the regulation of obesity-induced oxidative stress.
