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- Title
1,25-Dihydroxyvitamin D/vitamin D receptor suppresses brown adipocyte differentiation and mitochondrial respiration.
- Authors
Ricciardi, Carolyn; Bae, Jiyoung; Esposito, Debora; Komarnytsky, Slavko; Hu, Pan; Chen, Jiangang; Zhao, Ling
- Abstract
Purpose: The vitamin D system plays a role in metabolism regulation. 1,25-dihydroxyvitamin D (1,25(OH)D) 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)D/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)D 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)D 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)D and VDR over-expression suppressed PPARγ transactivation in brown preadipocytes. Conclusion: Our results demonstrate the suppressive effects of 1,25(OH)D/VDR signaling on brown adipocyte differentiation and mitochondrial respiration. The role of 1,25(OH)D/VDR system in regulating BAT development and function in obesity warrant further investigation.
- Subjects
TENNESSEE; MITOCHONDRIAL physiology; PROTEIN metabolism; RNA metabolism; ENZYME metabolism; OXYGEN metabolism; ANIMAL experimentation; BIOLOGICAL assay; BIOLOGICAL models; BIOPHYSICS; CELL physiology; CELL receptors; CELLULAR signal transduction; DOSE-response relationship in biochemistry; FAT cells; RESEARCH methodology; MICE; OBESITY; POLYMERASE chain reaction; PROBABILITY theory; STAINS &; staining (Microscopy); STATISTICS; T-test (Statistics); WESTERN immunoblotting; DATA analysis; REPEATED measures design; DATA analysis software; PEROXISOME proliferator-activated receptors; CALCITRIOL; DESCRIPTIVE statistics; IN vitro studies; ONE-way analysis of variance
- Publication
European Journal of Nutrition, 2015, Vol 54, Issue 6, p1001
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-014-0778-9