Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice

J Biol Chem. 2011 Sep 30;286(39):33804-10. doi: 10.1074/jbc.M111.257568. Epub 2011 Aug 12.


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.

Publication types

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

MeSH terms

  • 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 / genetics
  • Locomotion / genetics
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • Organ Specificity
  • Oxidation-Reduction
  • Promoter Regions, Genetic / genetics
  • Receptors, Calcitriol / biosynthesis*
  • Receptors, Calcitriol / genetics
  • Thermogenesis / genetics


  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Receptors, Calcitriol