Premium
Microarray analysis of the effects of calcitriol and cortisone on human adipocyte gene expression
Author(s) -
Morris Kristin,
Sun Xiaocun,
Zemel Michael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1119-a
Subject(s) - calcitriol , endocrinology , adipocyte , medicine , downregulation and upregulation , adiponectin , adipose tissue , cortisone , chemistry , biology , vitamin d and neurology , insulin , insulin resistance , gene , biochemistry
Dietary calcium inhibits adiposity in both mice and humans. A key underlying mechanism is suppression of calcitriol, which modulates Ca 2+ signaling and mitochondrial uncoupling in adipocytes. We also demonstrated that calcitriol directly regulates adipocyte 11β‐HSD 1 expression and cortisol production in human adipocytes in vitro and dietary calcium inhibits visceral adipose tissue 11β‐HSD 1 expression in mice, indicating an interaction of calcitriol and cortisol in obesity. Consequently, we have evaluated the gene expression profile of human adipocytes treated with calcitriol and/or cortisone for 48 h. Analysis of the Affymetrix microarray data 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 upregulated genes involved in oxidative stress and inflammation such as NOX 4 and TLR‐3. The calcitriol/cortisone combination resulted in significant additional upregulation of 11β‐HSD 1 and downregulation 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.