Effects of High Fat Diet-Induced Obesity on Expression of Vitamin D Metabolizing Enzymes in Mice

Abstract

Low serum 25-hydroxyvitamin D (25(OH)D) concentration has been often reported in obese human. Lifestyle factors such as inadequate sun exposure and physiological factors such as impaired hepatic 25-hydroxylation have been suggested as possible explanations for vitamin D deficiency in obesity, however, the precise mechanism has not been elucidated. We investigated the effects of obesity on vitamin D status and the expression of vitamin D metabolizing enzymes using high fat diet-induced obese mice in order to understand the underlying mechanisms of altered vitamin D metabolism as-sociated with obesity. Four-wk-old C57BL/6 mice were fed control diet containing 10% energy fat (control group) or high fat diet with 45% energy fat (obese group) for 18 weeks. There was no difference in serum 25(OH)D concentration between groups while serum 1,25-dihydroxyvitamin D (1,25(OH)2D) concentration was significantly higher in obese mice. Hepatic mRNA levels of 25-hydroxylases (Cyp2r1, Cyp27a1 and Cyp2j3) were low-er in obese group, but CYP27A1 protein expression did not differ between groups. Renal 1α-hydroxylase (Cyp27b1) mRNA level was upregulated and 24-hydroxylase (Cyp24) mRNA level was downregulated in obese group. Serum 1,25(OH)2D concentration correlated positively with renal Cyp27b1 expression level and negatively with renal Cyp24 expression level. No dif-ference in serum calcium level was observed between groups, but serum par-athyroid hormone (PTH) concentration was higher in obese mice. Serum concentration of PTH correlated positively with body weight. In visceral adipose tissue, mRNA levels of 25-hydroxylases, Cyp27a1 and Cyp2j3, and vitamin D receptor (Vdr) were higher in obese mice. Overall, the expression of vitamin D metabolizing enzymes was influenced by high fat diet-induced obesity, which might partly explain the mechanisms of altered vitamin D en-docrine system in obesity. Higher concentration of serum PTH and 1,25(OH)2D in obese mice suggests abnormal regulation of serum 1,25(OH)2D concentrations by secondary hyperparathyroidism, which might have contributed to lower hepatic 25-hydroxylase mRNA levels. Higher mRNA expression of Vdr in adipose tissue might suggest the possibility of enhanced nonclassic functions by the interaction between 1,25(OH)2D and VDR in adipose tissue.