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Keywords:

  • 1, 25-dihydroxyvitamin D3;
  • 11β-hydroxysteroid dehydrogenase;
  • adipocytes;
  • [Ca2+]i

Abstract

Objective: 1, 25-Dihydroxyvitamin D3 dose dependently increases intracellular calcium in human adipocytes. We have demonstrated that suppression of circulating 1, 25-dihydroxyvitamin D3 levels by increasing dietary calcium reduces adipocyte intracellular calcium and reduces adiposity in both humans and rodents, with preferential loss of trunk fat. Autocrine production of cortisol by adipocytes of mice overexpressing 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1) in adipose tissue increases visceral adiposity, whereas knockout of 11β-HSD 1 appears to attenuate truncal obesity. Accordingly, our objective was to investigate the role of 1, 25-dihydroxyvitamin D3 in the modulation of adipocyte glucocorticoid metabolism.

Research Methods and Procedures: We examined the effect of 1, 25-dihydroxyvitamin D3 or angiotensin II on cortisol production and expression using real-time reverse transcriptase-polymerase chain reaction of 11β-HSD 1, angiotensin II receptor type 1 (AT1), and AT2 receptor in human adipocytes.

Results: Adipocytes produced negligible cortisol in the absence of substrate (cortisone). In the presence of cortisone (1 to 10 nM), there was significant cortisol production, which was dose dependently augmented (2- to 6-fold, p < 0.001) by 1, 25-dihydroxyvitamin D3 (0.1 to 10 nM). 1, 25-Dihydroxyvitamin D3 dose dependently increased 11β-HSD 1 expression up to 2-fold (p < 0.01) in both the presence and absence of cortisone. In contrast, 1, 25-dihydroxyvitamin D3 dose dependently decreased adipocyte AT1 expression (by 30% to 50%, p < 0.001) in both the presence and absence of cortisone, suggesting compensatory down-regulation of AT1.

Discussion: We conclude that 1, 25-dihydroxyvitamin D3 directly regulates adipocyte 11β-HSD 1 expression and, consequently, local cortisol levels and that this may contribute to the preferential loss of visceral adiposity by high-calcium diets.