1alpha,25-Dihydroxyvitamin D hydroxylase in adipocytes.

1alpha,25-Dihydroxyvitamin D hydroxylase in adipocytes.
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DOI:
10.1016/j.jsbmb.2008.09.006
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发表时间:
2008-11
影响因子:
4.1
通讯作者:
Teegarden, Dorothy
Teegarden, Dorothy
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Jia;Byrne, Mary E.;Chang, Eugene;Jiang, Yan;Donkin, Shawn S.;Buhman, Kimberly K.;Burgess, John R.;Teegarden, Dorothy

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高维生素D摄入量与胰岛素抵抗降低有关。肾外1α,25-二羟基维生素D羟化酶(1α-羟化酶)在几种组织中表达,有助于从底物25-羟基维生素D(25 OHD)局部合成1α,25-二羟基维生素D3(1,25(OH)2D)。尚未评估1α-羟化酶在与能量代谢相关的组织(包括脂肪组织)中的表达和饮食调节。将雄性Wistar大鼠喂食高钙(1.5%)和高维生素D(10,000 IU/kg)或低钙(0.25%),低维生素D(400 IU/kg),高脂肪(40%能量)或高蔗糖(66%能量)饮食背景14周。通过真实的时间PCR检测,在脂肪组织中检测到1α-羟化酶的表达,并且与膳食钙和维生素D水平没有差异。在3 T3-L1前脂肪细胞中也检测到1α-羟化酶mRNA,10 nM水平的25 OHD处理诱导了1,25(OH)2D反应基因CYP 24,并且在存在p450抑制剂酮康唑的情况下,该反应降低。此外,在完整的3 T3-L1前脂肪细胞中,3 H 25 OHD转化为3 H 1,25(OH)2D。这些结果累积表明,1α-羟化酶在脂肪组织中表达,并在培养的脂肪细胞中发挥功能。因此,局部生产能力可能在调节脂肪细胞生长和代谢中发挥作用。
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.
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