OBJECTIVE: Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. METHODS: Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1a-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. RESULTS: A plasma 25OHD level o50 nmol l À 1 was highly prevalent in both lean (45%) and obese (90%) women (Po0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (Po0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 were decreased by 71% (Po0.0001) and 49% (Po0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (Po0.05) after weight loss. CONCLUSION: Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss.
INTRODUCTIONLow levels of circulating 25-hydroxy-vitamin D (25OHD) are associated with increased fat mass and body mass index, 1-5 but the underlying mechanism for this association is not fully elucidated. 6 Vitamin D (VD) is stored in adipose tissue (AT), and release of VD from AT is proposed to serve as an endogenous source of VD during the winter, when cutaneous production is low or absent in several parts of the world. 7 As low circulating levels of 25OHD are common in association with the obese state, 8 several studies have examined the effect of weight loss on circulating levels of 25OHD. However, results are inconsistent. After diet-and exercise-induced weight loss, both increased 9-11 and unaltered 12,13 circulating levels of 25OHD have been reported. Likewise, after major weight loss by bariatric surgery, both temporary 14-16 and long-term increases [16][17][18] in circulating levels of 25OHD have been reported, along with reports of no changes one year after surgery. 13,19 Taken together, these findings indicate that body weight is an important factor for circulating 25OHD levels. Several other explanations for the low levels of 25OHD in obesity have been proposed: a decreased exposure to sun light, 20 ...
