|Jung, Young Sun - Seoul National University|
|Wu, Dayong - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Smith, Donald - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Meydani, Simin - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Han, Sung Nim - Seoul National University|
Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2018
Publication Date: 5/1/2018
Citation: Jung, Y., Wu, D., Smith, D.E., Meydani, S.N., Han, S. 2018. Dysregulated 1,25-dihydroxyvitamin D levels in high fat diet-induced obesity can be restored by changing to a lower fat diet in mice. Nutrition Research. 53:51-60.
Interpretive Summary: Obesity is often associated with vitamin D deficiency in humans. According to a recent review of several vitamin D studies, the prevalence of vitamin D deficiency in obese humans was 35 percent higher than in non-obese humans. An abnormally regulated active form of vitamin D and high levels of a hormone associated with vitamin D deficiency have been observed in obese individuals as well. In mice, higher levels of both markers have been observed in conjunction with obesity. In the current study, we investigated whether altered vitamin D metabolism in obese mice could be reversed by the weight and fat loss associated with switching the mice from a high fat diet to a low fat diet. Vitamin D metabolism in kidneys was restored after reducing fat mass. In the current study, we demonstrated that changes in fat mass and vitamin D metabolism associated with high fat diet-induced obesity could be reversed by switching mice to a lower fat diet. Our study results indicate that practicing weight control to avoid obesity is one way to prevent vitamin D deficiency.
Technical Abstract: Altered regulation of major vitamin D metabolites, 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D), were observed in high fat diet (HFD)-induced obesity. We investigated whether HFD-induced changes in vitamin D metabolism could be reversed by decreasing fat mass by changing from a HFD to a lower fat diet. Four-week-old C57BL/6 mice were assigned to LL, HH, or HL groups after 5 days of acclimation. LL group was fed control diet (low fat) for 31 weeks, HH group was fed HFD for 31 weeks, and HL group was fed HFD for 15 weeks then switched to the control diet for the remaining 16 weeks. Body weight and fat mass were significantly different among groups (fat mass were 11.4 g in LL, 15.8 g in HL, and 37.5 g in HH). Serum 1,25(OH)2D levels were significantly higher in HH than LL group, while that of HL group was in intermediate to the two groups. Serum parathyroid hormone levels showed a significantly positive association with body adiposity (r=0.622). Renal 1-hydroxylase mRNA levels were significantly higher in HH group compared with LL and HL groups. No significant difference was found in serum 25(OH)D levels and mRNA levels of hepatic 25-hydroxylases. Renal Lrp2 mRNA levels showed a significantly negative correlation with fat mass (r=-0.538). In adipose tissue, mRNA levels of 25-hydroxylases and Vdr were elevated according to the degree of adiposity. In conclusion, reducing body adiposity by switching to a lower fat diet can partially restore altered vitamin D metabolism in HFD-induced obesity in mice.