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The Adipocyte Renin Angiotensin System (RAS) Mediates the Effects of Calcitriol on Oxidative Stress and Cytokine Expression
Author(s) -
Caserio Christina M,
Zemel Michael B
Publication year - 2008
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.22.1_supplement.700.31
Subject(s) - calcitriol , nox4 , endocrinology , medicine , adipocyte , chemistry , oxidative stress , angiotensin ii , adiponectin , reactive oxygen species , antagonism , nadph oxidase , receptor , biology , biochemistry , adipose tissue , insulin , vitamin d and neurology , insulin resistance
We recently demonstrated calcitriol to stimulate adipocyte reactive oxygen species (ROS) production and inflammatory stress (IS), while dietary calcium suppression of calcitriol exerted the opposite effect. These effects are mediated, in part, by calcitriol modulation of Ca 2+ signaling and mitochondrial potential. However, adipocytes contain a functional RAS, and angiotensin II (AT) modulates ROS and IS. Accordingly, we investigated the role of AT in mediating calcitriol effects. Calcitriol (1 nM) stimulated NOX4 expression and ROS production in 3T3‐L1 adipocytes by 67% (p<0.01), while these effects were reversed by ACE inhibition (enalapril) or antagonism of either AT receptor1 (AT1R) or AT2R, antagonism. Similarly, AT (0.1 – 1.0 nM) stimulated NOX4 expression (p<0.03), and this effect was reversed by AT1R or AT2R antagonism. Calcitriol and AT both suppressed adiponectin expression (p<0.04) and increased IL6 and MCP‐1 expression ∼ 2‐fold (p<0.03), and these effects were reversed with enalapril or AT2R, but not AT1R, antagonism. These data demonstrate that calcitriol modulation of adipocyte ROS production and IS is modulated, in part, by the adipocyte RAS.