The Suppressive Effects of 1,25-dihydroxyvitamin D3 and Vitamin D Receptor on Brown Adipocyte Differentiation and Mitochondrial Respiration

Author

Carolyn Jeanne Ricciardi, University of Tennessee - KnoxvilleFollow

Date of Award

8-2014

Degree Type

Thesis

Degree Name

Master of Science

Major

Nutrition

Major Professor

Ling Zhao

Committee Members

Jay Whelan, Guoxun Chen

Abstract

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.

Recommended Citation

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.
https://trace.tennessee.edu/utk_gradthes/2876