1α,25-Dihydroxyvitamin D hydroxylase in adipocytes

High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1α,25-dihydroxyvitamin D hydroxylase (1α-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1α-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 (10,000 IU/kg) or a low calcium (0.25%), low vitamin D (400 IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of 1α-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1α-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10 nM levels induced 1,25(OH)2D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, 3H 25OHD was converted to 3H 1,25(OH)2D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1α-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.