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European Journal of Nutrition

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01-09-2015 | Original Contribution

1,25-Dihydroxyvitamin D₃/vitamin D receptor suppresses brown adipocyte differentiation and mitochondrial respiration

Authors: Carolyn J. Ricciardi, Jiyoung Bae, Debora Esposito, Slavko Komarnytsky, Pan Hu, Jiangang Chen, Ling Zhao

Published in: European Journal of Nutrition | Issue 6/2015

Abstract

Purpose

The vitamin D system plays a role in metabolism regulation. 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) suppressed 3T3-L1 white 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), now known to be present in adult humans, functions in non-shivering thermogenesis by uncoupling ATP synthesis from respiration and plays an important role in energy expenditure. However, the effects of 1,25(OH)₂D₃/VDR on brown adipocyte differentiation and mitochondrial respiration have not been reported.

Methods

mRNA expression of VDR and the metabolizing enzymes 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1) were examined in BAT of mice models of obesity and during brown adipocyte differentiation. The effects of 1,25(OH)₂D₃ and VDR over-expression on brown adipocyte differentiation and functional outcomes were evaluated.

Results

No significant changes in mRNA of VDR and CYP27B1 were noted in both diet-induced obese (DIO) and ob/ob mice, whereas uncoupling protein 1 mRNA was downregulated in BAT of ob/ob, but not DIO mice when compared to the controls. In contrast, mRNA of VDR, CYP24A1, and CYP27B1 were downregulated during brown adipocyte differentiation in vitro. 1,25(OH)₂D₃ dose-dependently suppressed brown adipocyte differentiation, accompanied by suppressed isoproterenol-stimulated oxygen consumption rates (OCR), maximal OCR and OCR from proton leak. Consistently, over-expression of VDR also suppressed brown adipocyte differentiation. Further, both 1,25(OH)₂D₃ and VDR over-expression suppressed PPARγ transactivation in brown preadipocytes.

Conclusion

Our results demonstrate the suppressive effects of 1,25(OH)₂D₃/VDR signaling on brown adipocyte differentiation and mitochondrial respiration. The role of 1,25(OH)₂D₃/VDR system in regulating BAT development and function in obesity warrant further investigation.

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Title: 1,25-Dihydroxyvitamin D3/vitamin D receptor suppresses brown adipocyte differentiation and mitochondrial respiration
Authors: Carolyn J. Ricciardi
Jiyoung Bae
Debora Esposito
Slavko Komarnytsky
Pan Hu
Jiangang Chen
Ling Zhao
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 6/2015
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-014-0778-9

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1,25-Dihydroxyvitamin D₃/vitamin D receptor suppresses brown adipocyte differentiation and mitochondrial respiration

Abstract

Purpose

Methods

Results

Conclusion

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