1Alpha,25-dihydroxyvitamin D3 modulation of adipocyte reactive oxygen species production |
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Authors: | Sun Xiaocun Zemel Michael B |
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Institution: | Department of Nutrition, University of Tennessee, 1215 West Cumberland Avenue, #229, Knoxville, TN 37996-1900, USA. |
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Abstract: | Objective: We have previously shown 1α,25‐dihydroxyvitamin D3 1α,25‐(OH)2D3] to inhibit mitochondrial uncoupling protein 2 (UCP2) expression in adipocytes and that in vivo suppression of calcitriol levels with calcium‐rich diets increases UCP2 expression. Because UCP2 plays a significant role in the clearance of reactive oxygen species (ROS), we studied the effect of calcitriol on ROS production and ROS‐induced adipocyte proliferation. Research Methods and Procedures: ROS production in human and murine adipocytes was stimulated by high glucose (30 mM) or H2O2 (100 nM). Results: Both approaches resulted in increased ROS production by 27% to 100% (p < 0.05) and increased cell proliferation by 15% to 39% (p < 0.03). These effects were augmented by the addition of mitochondrial uncoupling inhibitor guanosine 5′‐diphosphate (GDP; 100 μM) or 1α,25‐(OH)2D3 (10 nM) and attenuated by UCP2 overexpression, suggesting that inhibition of mitochondrial uncoupling suppresses clearance of ROS and increases adipocyte proliferation. The addition of α ± tocopherol (1 μM) inhibited cell proliferation in adipocytes treated with either H2O2 or high glucose, indicating that ROS plays a major role in the regulation of cell proliferation in adipocytes. Moreover, stimulation of ROS with high glucose and H2O2 resulted in a 2‐ to 5‐fold increase in adipocyte intracellular calcium (Ca2+]i; p < 0.001), and calcium channel antagonism (nifedipine, 10 μM) suppressed ROS induced calcium influx and cell proliferation, indicating that Ca2+]i may also regulate ROS production and exert a mitogenic effect in adipocytes. Discussion: These data support a role of 1α,25‐(OH)2D3, UCP2, and Ca2+]i in the regulation of adipocyte ROS production. |
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Keywords: | calcitriol calcium reactive oxygen species uncoupling protein 2 |
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