Date of Award
Master of Science
Jay Whelan, Guoxun Chen
The vitamin D system plays a role in metabolism regulation. It has been reported that 1,25(OH)2D3 [1,25-dihydroxyvitamin D] suppresses 3T3-L1 adipocyte differentiation. Vitamin D receptor (VDR) knockout mice showed increased energy expenditure whereas mice with adipose-specific VDR over expression showed decreased energy expenditure. Brown adipose tissue (BAT), which functions in non-shivering thermogenesis by uncoupling ATP synthesis from oxidation, plays important roles in energy expenditure. However, the effects of 1,25(OH)2D3 on brown adipocyte differentiation and mitochondrial respiration have not been studied. Reported here is the mRNA expression of VDR, UCP1, and CYP27B1 (1α[alpha]- hydroxylase) in two mice models of obesity; and the down regulation of mRNA of VDR, CYP24A1 (24-hyrdoxylase), and CYP27B1 during brown adipocyte differentiation in vitro. 1,25(OH)2D3 dose-dependently suppressed brown adipocyte differentiation, as revealed by oil red O (ORO) stained cell morphology, ORO absorbance, and brown adipocyte marker gene expression. Moreover, cellular bioenergetics measurements showed that 1,25(OH)2D3 suppressed isoproterenol-stimulated oxygen consumption rates (OCR), maximal OCR and OCR from proton leak, but had no effects on ATP-generating OCR and spare respiration capacity in brown adipocytes. Consistently, over-expression of VDR also suppressed brown adipocyte differentiation. Furthermore, both 1,25(OH)2D3 and VDR over expression suppressed PPARγ[gamma] transactivation in brown preadipocytes. Taken together, the results demonstrate the suppressive effects of 1,25(OH)2D3/VDR signaling on brown adipocyte differentiation and mitochondrial respiration and suggest a role of 1,25(OH)2D3/VDR signaling in regulating BAT function for obesity treatment and prevention.
Ricciardi, Carolyn Jeanne, "The Suppressive Effects of 1,25-dihydroxyvitamin D3 and Vitamin D Receptor on Brown Adipocyte Differentiation and Mitochondrial Respiration. " Master's Thesis, University of Tennessee, 2014.