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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/E820    most recent 90763.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wong, K. E. Articles by Li, Y. C. Search for Related Content PubMed PubMed Citation Articles by Wong, K. E. Articles by Li, Y. C.

Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins

Division of Biological Sciences, Department of Medicine, Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois

Submitted 10 September 2008 ; accepted in final form 22 January 2009

Recent studies have established that vitamin D plays multiple biological roles beyond calcium metabolism; however, whether vitamin D is involved in energy metabolism is unknown. To address this question, we characterized the metabolic phenotypes of vitamin D receptor (VDR)-null mutant mice. Under a normocalcemic condition, VDR-null mice displayed less body fat mass and lower plasma triglyceride and cholesterol levels compared with wild-type (WT) mice; when placed on a high-fat diet, VDR-null mice showed a slower growth rate and accumulated less fat mass globally than WT mice, even though their food intake and intestinal lipid transport capacity were the same as WT mice. Consistent with the lower adipose mass, plasma leptin levels were lower and white adipocytes were histologically smaller in VDR-null mice than WT mice. The rate of fatty acid β-oxidation in the white adipose tissue was higher, and the expression of uncoupling protein (UCP) 1, UCP2 and UCP3 was markedly upregulated in VDR-null mice, suggesting a higher energy expenditure in the mutant mice. Experiments using primary brown fat culture confirmed that 1,25-dihydroxyvitamin D₃ directly suppressed the expression of the UCPs. Consistently, the energy expenditure, oxygen consumption, and CO₂ production in VDR-null mice were markedly higher than in WT mice. These data indicate that vitamin D is involved in energy metabolism and adipocyte biology in vivo in part through regulation of β-oxidation and UCP expression.

adipocytes; uncoupling proteins; energy metabolism