1α,25-Dihydroxyvitamin D hydroxylase in adipocytes

Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.
The Journal of Steroid Biochemistry and Molecular Biology (Impact Factor: 3.63). 10/2008; 112(1-3):122-6. DOI: 10.1016/j.jsbmb.2008.09.006
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High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1alpha,25-dihydroxyvitamin D hydroxylase (1alpha-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1alpha-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 1alpha-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1alpha-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10nM 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, (3)H 25OHD was converted to (3)H 1,25(OH)(2)D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1alpha-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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Available from: Yan Jiang, Oct 06, 2015
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    • "One of these is adipose tissue, which is an important metabolic organ having a central role in energy balance and glucose homeostasis [8]. Adipose tissue is not only the major organ for vitamin D storage [9], but also expresses the vitamin D receptor (VDR) [10] and enzymes for vitamin D metabolism [11]. In the mouse preadipocyte model 3T3-L1, 1,25(OH) 2 D 3 inhibits adipogenesis [12] [13], and also in the human Simpson–Golabi–Behmel syndrome (SGBS) preadipocyte model, vitamin D 3 metabolites modulate the differentiation process [10] [14]. "
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    ABSTRACT: Scope: Vitamin D₃, its biologically most active metabolite 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), and the vitamin D receptor (VDR) are important for adipose tissue biology. Methods and results: We extrapolated genomic VDR association loci in adipocytes from 55 conserved genome-wide VDR-binding sites in nonfat tissues. Taking the genes DUSP10, TRAK1, NRIP1, and THBD as examples, we confirmed the predicted VDR binding sites upstream of their transcription start sites and showed rapid mRNA up-regulation of all four genes in SGBS human pre-adipocytes. Using adipose tissue biopsy samples from 47 participants of a 5-month vitamin D₃ intervention study, we demonstrated that all four primary VDR target genes can serve as biomarkers for the vitamin D₃ responsiveness of human individuals. Changes in DUSP10 gene expression appear to be the most comprehensive marker, while THBD mRNA changes characterized a rather different group of study participants. Conclusion: We present a new approach to predict vitamin D target genes based on conserved genomic VDR-binding sites. Using human adipocytes as examples, we show that such ubiquitous VDR target genes can be used as markers for the individual's response to a supplementation with vitamin D₃.
    Molecular Nutrition & Food Research 10/2014; 58(10). DOI:10.1002/mnfr.201400291 · 4.60 Impact Factor
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    • "It has been clearly shown that adipose tissue may both regulate and be regulated by vitamin D [45]. The expression of the vitamin D receptor, 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes, and 24-hydroxylase enzyme has been shown in human adipocytes [46]. There are some experimental data suggesting that vitamin D could promote greater adiposity, leading to elevated parathyroid hormone, which may promote calcium influx into adipocytes thereby enhancing lipogenesis [47]. "
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    ABSTRACT: The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function.
    International Journal of Endocrinology 08/2014; 2014:841248. DOI:10.1155/2014/841248 · 1.95 Impact Factor
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    • "The first recognition of an extrarenal vitamin D system dates back more than twenty-five years ago, following studies of vitamin D metabolism in pregnancy [83] and granulomatous disease sarcoidosis [84]. Afterwards, some studies with knockout mice have demonstrated the expression of CYP27B1 in several other tissues, including skin [85], prostate [86], brain [87], pancreas [88], adipose tissue [89], skeletal muscle [90], heart [91], colon [92], and neoplastic tissues [93]. In 2012, Schnatz and coworkers firstly recognized the expression of VDR within atherosclerotic plaques of premenopausal cynomolgus monkeys [94], also observing an interesting inverse correlation between plaque burden and serum 25(OH) vitamin D levels [95]. "
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    ABSTRACT: Vitamin D has been shown to play critical activities in several physiological pathways not involving the calcium/phosphorus homeostasis. The ubiquitous distribution of the vitamin D receptor that is expressed in a variety of human and mouse tissues has strongly supported research on these "nonclassical" activities of vitamin D. On the other hand, the recent discovery of the expression also for vitamin D-related enzymes (such as 25-hydroxyvitamin D-1 α -hydroxylase and the catabolic enzyme 1,25-dihydroxyvitamin D-24-hydroxylase) in several tissues suggested that the vitamin D system is more complex than previously shown and it may act within tissues through autocrine and paracrine pathways. This updated model of vitamin D axis within peripheral tissues has been particularly investigated in atherosclerotic pathophysiology. This review aims at updating the role of the local vitamin D within atherosclerotic plaques, providing an overview of both intracellular mechanisms and cell-to-cell interactions. In addition, clinical findings about the potential causal relationship between vitamin D deficiency and atherogenesis will be analysed and discussed.
    12/2013; 2013:620504. DOI:10.1155/2013/620504
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