Role of calcitriol and cortisol on human adipocyte proliferation and oxidative and inflammatory stress: a microarray study.
Dietary calcium inhibits adiposity, and a key underlying mechanism is suppression of calcitriol, which modulates Ca(2+) signaling and mitochondrial uncoupling in adipocytes. We demonstrated that calcitriol directly regulates adipocyte 11beta-HSD-1 expression and cortisol production in human adipocytes in vitro and dietary calcium inhibits visceral adipose tissue 11beta-HSD-1 expression in mice, indicating an interaction of calcitriol and cortisol in obesity. Consequently, we have evaluated the gene expression profile of human subcutaneous adipocytes treated with calcitriol and/or cortisone. Data analysis demonstrated significant calcitriol modulation of gene expression toward inhibition of the adipocyte apoptosis (e.g., VEGF and STC-2) and promotion of adipocyte proliferation (e.g., IGF-1 and IGF-1R). Calcitriol also up-regulated oxidative stress and inflammatory genes such as NOX-4 and TLR-3. The calcitriol/cortisone combination resulted in significant additional up-regulation of 11beta-HSD-1 and down-regulation of adiponectin expression, while cortisone exerted little independent effect in the absence of calcitriol. Overall, calcitriol stimulated a pattern of adipocyte gene expression which favored adipocyte proliferation, oxidative and inflammatory stress and visceral adiposity, and these effects were amplified in the presence of cortisone; however, this conclusion must be tempered by the adipocyte source (subcutaneous) and requires confirmation in visceral adipocytes.
Sun
Xiaocun
X
University of Tennessee, Knoxville, Tenn. 37996-1900, USA.
Morris
Kristin L
KL
Zemel
Michael B
MB
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D016133:Polymerase Chain Reaction
D002117:Calcitriol; D006854:Hydrocortisone