1α,25-Dihydroxyvitamin D hydroxylase in adipocytes

High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1 alpha,25-dihydroxyvitamin D hydroxylase (l(x-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D) from the substrate 25-hydroxyvitamin D (250HD). Expression and dietary regulation of 1 alpha-hydroxylase in tissues associated with energy metabolism, including adipose tissue, has not been assessed. Male Wistar rats were fed a high calcium (1.5%) and high vitamin D (10,000IU/kg) or a low calcium (0.25%), low vitamin D (400IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of lahydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1 alpha-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 250HD treatment at 10 nM levels induced 1,25(OH)(2)D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, H-3 25OHD was converted to H-3 1,25(OH)(2)D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that la-hydroxylase is expressed in adipose tissue and is functional in cultured adipocytes. Thus, the capacity for local production may play a role in regulating adipocyte growth and metabolism. (C) 2008 Elsevier Ltd. All rights reserved.