Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes

Nutrition. 2016 Jun;32(6):702-8. doi: 10.1016/j.nut.2015.12.032. Epub 2015 Dec 29.


Objective: Previous studies suggest that low vitamin D status is associated with obesity characterized by excess lipid storage in adipocytes. The aim of the present study was to determine the effects of the most hormonally active form of vitamin D 1,25-dihydroxyvitamin D [1,25(OH)2D] on adipocyte fat storage and lipid metabolism in mature 3T3-L1 cells.

Methods: Differentiated 3T3-L1 cells were treated with various concentrations of 1,25(OH)2D. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation, intracellular lipid content, and basal and isoproterenol-stimulated lipolysis were measured to investigate the regulatory role of 1,25(OH)2D in adipocyte lipid metabolism. Reverse transcription polymerase chain reaction was performed to determine the effects of 1,25(OH)2D on adipogenesis-related markers, fatty acid oxidation-associated genes, and lipolytic enzymes. Sirtulin 1 (SIRT1) activity, nicotinamide adenine dinucleotide (NAD) and NADH were measured.

Results: 1,25(OH)2D treatment (24 h, 100 nmol/L) induced a decrease in intracellular fat accumulation and an increase of basal and isoproterenol-stimulated lipolysis without cell toxicity in adipocytes. Adipogenic gene levels were decreased. In contrast, mRNA levels of β-oxidation-related genes, lipolytic enzymes, and vitamin D responsive gene were elevated by 1,25(OH)2D. Additionally, significant incremental changes in NAD levels, the ratio of NAD to NADH, and SIRT1 expression and activity were noted in 1,25(OH)2D-treated 3T3-L1 adipocytes.

Conclusions: The observed potent inhibitory effect of 1,25(OH)2D on adipocyte fat storage in mature 3T3-L1 cells suggests that vitamin D might improve adipocyte metabolic function and protect against obesity. Increased NAD concentrations and SIRT1 ​activity may play a role in the mechanism of 1,25(OH)2D action.

Keywords: 1,25(OH)2D; Adipocyte; Lipid storage; Lipolysis; NAD; Obesity; SIRT1.

MeSH terms

  • 3T3-L1 Cells / drug effects*
  • 3T3-L1 Cells / metabolism
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Animals
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression / genetics
  • Humans
  • Lipid Metabolism / drug effects*
  • Lipolysis / drug effects*
  • Mice
  • NAD / drug effects
  • NAD / genetics
  • NAD / metabolism
  • Oxidation-Reduction / drug effects
  • Polymerase Chain Reaction
  • Sirtuin 1 / drug effects*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology


  • NAD
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Sirt1 protein, mouse
  • Sirtuin 1