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Hormone Molecular Biology and Clinical Investigation

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Vitamin D metabolism in human adipose tissue: could it explain low vitamin D status in obesity?

Adryana Cordeiro
  • Micronutrients Research Center (NPqM), Institute of Nutrition Josué de Castro (INJC) of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
  • Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alejandro Santos
  • Faculty of Nutrition and Food Sciences, University of Porto (FCNAUP), 4200-465 Porto, Portugal
  • Institute for Research and Innovation in Health (i3s), University of Porto, 4200-135 Porto, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Miguel Bernardes
  • Department of Medicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
  • Rheumatology Department, São João Hospital Center, 4200-319 Porto, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andrea Ramalho
  • Micronutrients Research Center (NPqM), Institute of Nutrition Josué de Castro (INJC) of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
  • Social Applied Nutrition Department, Institute of Nutrition Josué de Castro (INJC) of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
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/ Maria João Martins
  • Corresponding author
  • Institute for Research and Innovation in Health (i3s), University of Porto, 4200-135 Porto, Portugal
  • Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal, Phone/Fax: +351225513624
  • Email
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Published Online: 2017-07-18 | DOI: https://doi.org/10.1515/hmbci-2017-0003


Obesity and a low vitamin D (VD) status, as well as a positive association between them, are prevalent worldwide. Additionally, a low VD status has been positively correlated with metabolic dysfunction (although not so convincingly as for obesity). The VD receptor (VDR) mediates VD biological actions in adipose tissue (AT), where VD can be activated or inactivated/degraded through specific hydroxylation steps. Additionally, AT can also store and release VD when needed. A lower VD activation/VD inactivation ratio and an impaired VDR signaling in AT could contribute to metabolic dysfunction besides the aforementioned association between obesity and VD status. However, subcutaneous (SAT) and visceral AT (VAT) are not expected to be similarly accountable as these two fat depots play differential roles in metabolic regulation/dysfunction. To our knowledge, only three articles disclose the evaluation of the expression of VDR and/or VD hydroxylating enzymes in human SAT and VAT. A clear dependence on the subcutaneous and/or the visceral fat depot is missing for the relationships of a) obesity and/or metabolic dysfunction with VD status and b) adipose VDR signaling and adipose VD activation/VD inactivation ratio with VD status, obesity and/or metabolic dysfunction. Further studies are warranted to unravel the influence of adipose VD metabolism on VD status.

Keywords: adiposity measures; insulin sensitivity and resistance; obesity; subcutaneous adipose tissue; visceral adipose tissue; vitamin D; vitamin D hydroxylation; vitamin D receptor

  • [1]

    Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, et al. Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr. 2009;90:459–67.CrossrefGoogle Scholar

  • [2]

    Kremer R, Campbell PP, Reinhardt T, Gilsanz V. Vitamin D status and its relationship to body fat, final height, and peak bone mass in young women. J Clin Endocrinol Metab. 2009;94:67–73.CrossrefGoogle Scholar

  • [3]

    Young KA, Engelman CD, Langefeld CD, Hairston KG, Haffner SM, Bryer-Ash M, et al. Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. J Clin Endocrinol Metab. 2009;94:3306–13.CrossrefGoogle Scholar

  • [4]

    Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, et al. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes. 2010;59:242–8.CrossrefGoogle Scholar

  • [5]

    Alvarez JA, Ashraf AP, Hunter GR, Gower BA. Serum 25-hydroxyvitamin D and parathyroid hormone are independent determinants of whole-body insulin sensitivity in women and may contribute to lower insulin sensitivity in African Americans. Am J Clin Nutr. 2010;92:1344–9.CrossrefGoogle Scholar

  • [6]

    Rajakumar K, de las Heras J, Chen TC, Lee S, Holick MF, Arslanian SA. Vitamin D status, adiposity, and lipids in Black American and Caucasian children. J Clin Endocrinol Metab. 2011;96:1560–7.CrossrefGoogle Scholar

  • [7]

    Rajakumar K, de las Heras J, Lee S, Holick MF, Arslanian SA. 25-hydroxyvitamin D concentrations and in vivo insulin sensitivity and beta-cell function relative to insulin sensitivity in Black and White youth. Diabetes Care. 2012;35:627–33.CrossrefGoogle Scholar

  • [8]

    Nguyen VT, Li X, Elli EF, Ayloo SM, Castellanos KJ, Fantuzzi G, et al. Vitamin D, inflammation, and relations to insulin resistance in premenopausal women with morbid obesity. Obesity (Silver Spring). 2015;23:1591–7.CrossrefGoogle Scholar

  • [9]

    Clemente-Postigo M, Munoz-Garach A, Serrano M, Garrido-Sanchez L, Bernal-Lopez MR, Fernandez-Garcia D, et al. Serum 25-hydroxyvitamin D and adipose tissue vitamin D receptor gene expression: relationship with obesity and type 2 diabetes. J Clin Endocrinol Metab. 2015;100:E591–5.Google Scholar

  • [10]

    Khan RJ, Riestra P, Gebreab SY, Wilson JG, Gaye A, Xu R, et al. Vitamin D receptor gene polymorphisms are associated with abdominal visceral adipose tissue volume and serum adipokine concentrations but not with body mass index or waist circumference in African Americans: the Jackson Heart Study. J Nutr. 2016;146:1476–82.CrossrefGoogle Scholar

  • [11]

    Wamberg L, Christiansen T, Paulsen SK, Fisker S, Rask P, Rejnmark L, et al. Expression of vitamin D-metabolizing enzymes in human adipose tissue - the effect of obesity and diet-induced weight loss. Int J Obes (Lond). 2013;37:651–7.CrossrefGoogle Scholar

  • [12]

    Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005;28:1228–30.CrossrefGoogle Scholar

  • [13]

    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.CrossrefGoogle Scholar

  • [14]

    Huh SY, Gordon CM. Vitamin D deficiency in children and adolescents: epidemiology, impact and treatment. Rev Endocr Metab Disord. 2008;9:161–70.CrossrefGoogle Scholar

  • [15]

    Weng FL, Shults J, Leonard MB, Stallings VA, Zemel BS. Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents. Am J Clin Nutr. 2007;86:150–8.Google Scholar

  • [16]

    Fry CM, Sanders TA. Vitamin D and risk of CVD: a review of the evidence. Proc Nutr Soc. 2015;74:245–57.CrossrefGoogle Scholar

  • [17]

    Landrier JF, Karkeni E, Marcotorchino J, Bonnet L, Tourniaire F. Vitamin D modulates adipose tissue biology: possible consequences for obesity?. Proc Nutr Soc. 2016;75:38–46.CrossrefGoogle Scholar

  • [18]

    Malmberg P, Karlsson T, Svensson H, Lonn M, Carlsson NG, Sandberg AS, et al. A new approach to measuring vitamin D in human adipose tissue using time-of-flight secondary ion mass spectrometry: a pilot study. J Photochem Photobiol B. 2014;138:295–301.CrossrefGoogle Scholar

  • [19]

    Wamberg L, Pedersen SB, Rejnmark L, Richelsen B. Causes of vitamin D deficiency and effect of vitamin D supplementation on metabolic complications in obesity: a review. Curr Obes Rep. 2015;4:429–40.CrossrefGoogle Scholar

  • [20]

    Blum M, Dolnikowski G, Seyoum E, Harris SS, Booth SL, Peterson J, et al. Vitamin D(3) in fat tissue. Endocrine. 2008;33:90–4.CrossrefGoogle Scholar

  • [21]

    Ding C, Gao D, Wilding J, Trayhurn P, Bing C. Vitamin D signalling in adipose tissue. Br J Nutr. 2012;108:1915–23.CrossrefGoogle Scholar

  • [22]

    Alemzadeh R, Kichler J, Babar G, Calhoun M. Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism. 2008;57:183–91.CrossrefGoogle Scholar

  • [23]

    Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94:26–34.CrossrefGoogle Scholar

  • [24]

    Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.CrossrefGoogle Scholar

  • [25]

    Gupta GK, Agrawal T, DelCore MG, Mohiuddin SM, Agrawal DK. Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine. Exp Mol Pathol. 2012;93:82–90.CrossrefGoogle Scholar

  • [26]

    Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80:1678S–88.Google Scholar

  • [27]

    Kong J, Li YC. Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am J Physiol Endocrinol Metab. 2006;290:E916–24.Google Scholar

  • [28]

    Martini LA, Wood RJ. Vitamin D status and the metabolic syndrome. Nutr Rev. 2006;64:479–86.CrossrefGoogle Scholar

  • [29]

    Shen L, Zhuang QS, Ji HF. Assessment of vitamin D levels in type 1 and type 2 diabetes patients: results from metaanalysis. Mol Nutr Food Res. 2016;60:1059–67.CrossrefGoogle Scholar

  • [30]

    Trochoutsou AI, Kloukina V, Samitas K, Xanthou G. Vitamin-D in the immune system: genomic and non-genomic actions. Mini Rev Med Chem. 2015;15:953–63.CrossrefGoogle Scholar

  • [31]

    Ulutas O, Taskapan H, Taskapan MC, Temel I. Vitamin D deficiency, insulin resistance, serum adipokine, and leptin levels in peritoneal dialysis patients. Int Urol Nephrol. 2013;45:879–84.CrossrefGoogle Scholar

  • [32]

    Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008;4:404–12.CrossrefGoogle Scholar

  • [33]

    Jablonski KL, Chonchol M, Pierce GL, Walker AE, Seals DR. 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension. 2011;57:63–9.CrossrefGoogle Scholar

  • [34]

    Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015;74:115–24.CrossrefGoogle Scholar

  • [35]

    Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72:690–3.Google Scholar

  • [36]

    Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring). 2012;20:1444–8.CrossrefGoogle Scholar

  • [37]

    Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Vitamin D receptor (VDR)-mediated actions of 1alpha,25(OH)(2)vitamin D(3): genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab. 2011;25:543–59.CrossrefGoogle Scholar

  • [38]

    Carr MC, Brunzell JD. Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. J Clin Endocrinol Metab. 2004;89:2601–7.CrossrefGoogle Scholar

  • [39]

    Fan JG, Farrell GC. VAT fat is bad for the liver, SAT fat is not!. J Gastroenterol Hepatol. 2008;23:829–32.CrossrefGoogle Scholar

  • [40]

    Lemieux S. Contribution of visceral obesity to the insulin resistance syndrome. Can J Appl Physiol. 2001;26:273–90.CrossrefGoogle Scholar

  • [41]

    Kato S. The function of vitamin D receptor in vitamin D action. J Biochem. 2000;127:717–22.CrossrefGoogle Scholar

  • [42]

    Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology. 2006;147:5542–8.CrossrefGoogle Scholar

  • [43]

    Zhao Y, Liao S, He J, Jin Y, Fu H, Chen X, et al. Association of vitamin D receptor gene polymorphisms with metabolic syndrome: a case-control design of population-based cross-sectional study in North China. Lipids Health Dis. 2014;13:129.CrossrefGoogle Scholar

  • [44]

    Beydoun MA, Tanaka T, Beydoun HA, Ding EL, Ferrucci L, Zonderman AB. Vitamin D receptor and megalin gene polymorphisms are associated with central adiposity status and changes among US adults. J Nutr Sci. 2013;2:e33.CrossrefGoogle Scholar

  • [45]

    Cheon CK, Nam HK, Lee KH, Kim SY, Song JS, Kim C. Vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in a Korean population. Pediatr Int. 2015;57:870–4.CrossrefGoogle Scholar

  • [46]

    Filus A, Trzmiel A, Kuliczkowska-Plaksej J, Tworowska U, Jedrzejuk D, Milewicz A, et al. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male. 2008;11:134–9.CrossrefGoogle Scholar

  • [47]

    Li L, Wu B, Liu JY, Yang LB. Vitamin D receptor gene polymorphisms and type 2 diabetes: a meta-analysis. Arch Med Res. 2013;44:235–41.CrossrefGoogle Scholar

  • [48]

    Ochs-Balcom HM, Chennamaneni R, Millen AE, Shields PG, Marian C, Trevisan M, et al. Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes. Am J Clin Nutr. 2011;93:5–10.CrossrefGoogle Scholar

  • [49]

    Schuch NJ, Garcia VC, Vivolo SR, Martini LA. Relationship between vitamin D receptor gene polymorphisms and the components of metabolic syndrome. Nutr J. 2013;12:96.CrossrefGoogle Scholar

  • [50]

    Ye WZ, Reis AF, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G. Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol. 2001;145:181–6.Google Scholar

  • [51]

    Taylor HA, Wilson JG, Jones DW, Sarpong DF, Srinivasan A, Garrison RJ, et al. Toward resolution of cardiovascular health disparities in African Americans: design and methods of the Jackson Heart Study. Ethn Dis. 2005;15:S6-4-17.Google Scholar

  • [52]

    Aiba I, Yamasaki T, Shinki T, Izumi S, Yamamoto K, Yamada S, et al. Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006;71:849–56.CrossrefGoogle Scholar

  • [53]

    Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003;278:38084–93.Google Scholar

  • [54]

    Gupta RP, Hollis BW, Patel SB, Patrick KS, Bell NH. CYP3A4 is a human microsomal vitamin D 25-hydroxylase. J Bone Miner Res. 2004;19:680–8.Google Scholar

  • [55]

    Jones G, Prosser DE, Kaufmann M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Arch Biochem Biophys. 2012;523:9–18.Google Scholar

  • [56]

    Schuster I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011;1814:186–99.Google Scholar

  • [57]

    Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Commun. 2004;324:451–7.Google Scholar

  • [58]

    Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86:888–94.Google Scholar

  • [59]

    Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004;101:7711–5.CrossrefGoogle Scholar

  • [60]

    Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury SW. The distribution and storage of vitamin D and its metabolites in human tissues. Clin Sci. 1972;43:413–31.CrossrefGoogle Scholar

  • [61]

    Pereira CD, Azevedo I, Monteiro R, Martins MJ. 11beta-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus. Diabetes Obes Metab. 2012;14:869–81.Google Scholar

About the article

aAlejandro Santos and Miguel Bernardes contributed equally to this review article.

Received: 2017-01-31

Accepted: 2017-04-22

Published Online: 2017-07-18

Author Statement

Research funding: The authors acknowledge the Brazilian National Council for Scientific and Technological Development (CNPq) and the Portuguese Foundation for Science and Technology (FCT; project reference: UID/BIM/04293/2013).

Conflict of interest: The authors state no conflict of interest.

Informed consent: Informed consent is not applicable.

Ethical approval: The conducted research is not related to either human or animal use.

Citation Information: Hormone Molecular Biology and Clinical Investigation, 20170003, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: https://doi.org/10.1515/hmbci-2017-0003.

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