Dietary calcium regulates ROS production in aP2-agouti transgenic mice on high-fat/high-sucrose diets.
OBJECTIVE
We have previously demonstrated that 1alpha, 25(OH)2D3 promotes adipocyte reactive oxygen species (ROS) production. We have now evaluated whether decreasing 1alpha, 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 11beta-hydroxysteroid dehydrogenase (11beta-HSD) expression in visceral adipose tissue by 39% (P=0.034). 11beta-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.


CONCLUSIONS
These data support a potential role for dietary calcium in the regulation of obesity-induced oxidative stress.
Sun
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Department of Nutrition, University of Tennessee, Knoxville, TN 37996-1900, USA.
Zemel
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MB
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002136:Calcium, Dietary / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage; D019422:Dietary Sucrose / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002136:Calcium, Dietary; D004041:Dietary Fats; D019422:Dietary Sucrose; D017382:Reactive Oxygen Species; D012313:RNA