Dysregulated 1,25-dihydroxyvitamin D levels in high-fat diet-induced obesity can be restored by changing to a lower-fat diet in mice

Nutr Res. 2018 May:53:51-60. doi: 10.1016/j.nutres.2018.03.008. Epub 2018 Mar 20.


Altered regulation of vitamin D metabolites, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25[OH]2D), was observed in high-fat diet (HFD)-induced obesity. We hypothesized that these HFD-induced changes in vitamin D metabolism would be reversed by decreasing fat mass through dietary intervention. Four-week-old C57BL/6J mice were assigned to 1 of 3 experimental diet groups: (1) the LL group was fed a control diet for 31 weeks, (2) the HH group was fed an HFD for 31 weeks, and (3) the HL group was fed HFD for 15 weeks then switched to the control diet for the remaining 16 weeks. The fat mass of the HL group decreased by 15% from the 14th to the 30th week. Serum 1,25(OH)2D level was significantly higher in the HH group than the LL group, whereas that of the HL group was intermediate to the 2 groups. Serum parathyroid hormone and renal 1-hydroxylase (Cyp27b1) mRNA levels, which are known to stimulate renal 1,25(OH)2D production, were significantly higher in the HH group than the LL group. After losing fat mass, the HL group had significantly lower renal Cyp27b1 mRNA levels than the HH group. No differences were found in serum 25-hydroxyvitamin D levels and mRNA levels of hepatic 25-hydroxylases. In adipose tissue, mRNA levels of 25-hydroxylase and vitamin D receptor were elevated in parallel to the adiposity. In conclusion, serum 1,25(OH)2D levels were closely associated with body adiposity, and reducing fat mass by changing to a lower-fat diet can reverse this obesity-associated increase in circulating 1,25(OH)2D levels.

Keywords: Diet modulation; Fat loss; Obesity; Parathyroid hormone; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adipose Tissue / metabolism*
  • Adiposity
  • Animals
  • Diet, Fat-Restricted*
  • Diet, High-Fat / adverse effects
  • Dietary Fats / administration & dosage*
  • Dietary Fats / adverse effects
  • Female
  • Kidney / metabolism*
  • Liver / metabolism
  • Mice, Inbred C57BL
  • Obesity / blood*
  • Obesity / etiology
  • Obesity / metabolism
  • Parathyroid Hormone / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Calcitriol / blood
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / diet therapy*


  • Dietary Fats
  • Parathyroid Hormone
  • RNA, Messenger
  • Receptors, Calcitriol
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase