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

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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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Acknowledgments

We thank the Cell Culture Core Facility, Plants for Human Health Institute for their technical assistance with cellular bioenergetics measurement.

Conflict of interest

All authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Nutrition, University of Tennessee, 1215 W. Cumberland Ave, Knoxville, TN, 37996, USA

    Carolyn J. Ricciardi, Jiyoung Bae, Pan Hu, Jiangang Chen & Ling Zhao

  2. Department of Public Health, University of Tennessee, Knoxville, TN, 37996, USA

    Jiangang Chen

  3. North Carolina Research Campus, Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, 28081, USA

    Debora Esposito & Slavko Komarnytsky

  4. Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, Raleigh, NC, 27607, USA

    Debora Esposito & Slavko Komarnytsky

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  1. Carolyn J. Ricciardi
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Correspondence to Ling Zhao.

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Ricciardi, C.J., Bae, J., Esposito, D. et al. 1,25-Dihydroxyvitamin D3/vitamin D receptor suppresses brown adipocyte differentiation and mitochondrial respiration. Eur J Nutr 54, 1001–1012 (2015). https://doi.org/10.1007/s00394-014-0778-9

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  • DOI: https://doi.org/10.1007/s00394-014-0778-9

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