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

Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E820-8. doi: 10.1152/ajpendo.90763.2008. Epub 2009 Jan 27.


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 beta-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 beta-oxidation and UCP expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / physiology
  • Animals
  • Cells, Cultured
  • Energy Metabolism / drug effects
  • Energy Metabolism / genetics*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Ion Channels / genetics*
  • Ion Channels / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Oxidation-Reduction / drug effects
  • Oxygen Consumption / genetics
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Receptors, Calcitriol / physiology*
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3
  • Vitamin D / pharmacology


  • Ion Channels
  • Mitochondrial Proteins
  • Receptors, Calcitriol
  • Ucp1 protein, mouse
  • Ucp2 protein, mouse
  • Ucp3 protein, mouse
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3
  • Vitamin D