Targeted Expression of Human Vitamin D Receptor in Adipocytes Decreases Energy Expenditure and Induces Obesity in Mice

Our previous studies demonstrated a high fat diet-resistant lean phenotype of vitamin D receptor (VDR)-null mutant mice mainly due to increased energy expenditure, suggesting an involvement of the VDR in energy metabolism. Here, we took a transgenic approach to further define the role of VDR in adip...

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Bibliographic Details
Published in:The Journal of biological chemistry 2011-09, Vol.286 (39), p.33804-33810
Main Authors: Wong, Kari E., Kong, Juan, Zhang, Wenshuo, Szeto, Frances L., Ye, Honggang, Deb, Dilip K., Brady, Matthew J., Li, Yan Chun
Format: Article
Language:English
Subjects:
Adipocyte
Adipocytes - metabolism
Adipocytes - physiology
Animals
Biological Transport, Active - genetics
Energy Metabolism
Fatty Acid-Binding Proteins - genetics
Fatty Acid-Binding Proteins - metabolism
Fatty Acids - metabolism
Gene Expression Regulation
Humans
Lipolysis
Lipolysis - genetics
Locomotion - genetics
Metabolism
Mice
Mice, Mutant Strains
Mice, Transgenic
Nuclear Receptors
Obesity - genetics
Obesity - metabolism
Obesity - pathology
Organ Specificity
Oxidation-Reduction
Promoter Regions, Genetic - genetics
Receptors, Calcitriol - biosynthesis
Receptors, Calcitriol - genetics
Thermogenesis - genetics
Vitamin D
Vitamin D Receptor
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Summary:Our previous studies demonstrated a high fat diet-resistant lean phenotype of vitamin D receptor (VDR)-null mutant mice mainly due to increased energy expenditure, suggesting an involvement of the VDR in energy metabolism. Here, we took a transgenic approach to further define the role of VDR in adipocyte biology. We used the aP2 gene promoter to target the expression of the human (h) VDR in adipocytes in mice. In contrast to the VDR-null mice, the aP2-hVDR Tg mice developed obesity compared with the wild-type counterparts without changes in food intake. The increase in fat mass was mainly due to markedly reduced energy expenditure, which was correlated with decreased locomotive activity and reduced fatty acid β-oxidation and lipolysis in the adipose tissue in the transgenic mice. Consistently, the expression of genes involved in the regulation of fatty acid transport, thermogenesis, and lipolysis were suppressed in the transgenic mice. Taken together, these data confirm an important role of the VDR in the regulation of energy metabolism.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.257568