Upregulated 1,25‐dihydorxyvitamin D in high fat diet‐induced obesity could be restored by feeding a low fat diet
Authors: Jung Young Sun , Wu Dayong , Smith Donald , Meydani Simin Nikbin , Han Sung Nim 
Published: June 2021

Previously, we showed that high fat diet (HFD)‐induced obesity altered expression of vitamin D metabolizing enzymes resulting in higher serum 1,25(OH)2D levels. In the current study, we determined whether the HFD‐induced changes in vitamin D metabolism could be restored by decreasing fat mass through changing from a HFD to a lower fat diet. Five‐week‐old female C57BL/6 mice were assigned to 3 groups: LL, HH, or HL. LL group was fed control diet containing 10% energy as fat and HH group was fed HFD containing 60% energy as fat for 31 weeks. HL group was fed HFD for 15 weeks then switched to the control diet for the following 16 weeks. Fat mass was measured by MRI. Serum levels of 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), and fibroblast factor 23 were determined by enzyme immunoassay. mRNA levels of hepatic 25‐hydroxylases (Cyp27a1, Cyp2r1, Cyp2j3), renal 1‐hydroxylase (Cyp27b1), 24‐hydorxylase (Cyp24a1), vitamin D receptor (Vdr), parathyroid hormone receptor (Pthr), and megalin, and gonadal 25‐hydoxylases and Vdr were measured by real‐time PCR. Renal CYP27B1 protein levels were determined by Western blot analysis. Body weight and fat mass were significantly different among three groups. HH group had higher body weight (63.1 ± 1.5 g) and fat mass (37.5 ± 1.1 g) than LL (35.8 ± 1.9 g and 11.4 ± 2.0 g, respectively) and HL (40.6 ± 1.3 g and 15.8 ± 1.0 g, respectively) groups. HH group had significantly higher concentration of serum 1,25(OH)2D (65.4 ± 10.1 pmol/L) than LL group (16.3 ± 1.7 pmol/L), while that in HL group (46.7 ± 9.0 pmol/L) was in between. HH group's serum PTH level was significantly higher than LL group (247% higher, p<0.05) and tended to be higher than HL group (162% higher, p=0.055). Renal Cyp27b1 mRNA level in HL group was similar to that in LL group, but significantly lower than HH group (47% lower, p<0.05). Renal Cyp27b1 mRNA level showed significantly positive correlations with weight and fat mass (r=0.615, p<0.05 and r=0.612, p<0.05, respectively). Renal Cyp24a1 mRNA levels were not significantly different among groups. No significant difference was found in serum 25(OH)D levels and mRNA levels of hepatic 25‐hydroxylases among the groups. Renal megalin mRNA level was lower in HH group than LL group (p<0.05). mRNA levels of 25‐hydroxylases (Cyp2r1 and Cyp2j3) in adipose tissue were higher in HH group compared with LL and HL groups (p<0.05 and p=0.053, respectively). In addition, Vdr mRNA level in adipose tissue was significantly higher in HH group compared with LL group, and Vdr expression in HL group was intermediate between LL and HH groups. In conclusion, HFD‐induced obesity results in altered vitamin D metabolism and increased concentration of serum 1,25(OH)2D. Decreasing fat mass in obese mice by switching from a HFD to a lower fat diet can restore the altered vitamin D metabolism.Support or Funding InformationSupported by the grant from the National Research Foundation (NRF) of Korea (NRF‐2010‐0024878) and USDA contract #58‐1950‐0‐014