Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Vitamin D regulation of adipogenesis and adipose tissue functions

  • Nimitphong, Hataikarn (Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University) ;
  • Park, Eunmi (Department of Food and Nutrition, Hannam University) ;
  • Lee, Mi-Jeong (Department of Human Nutrition, Food and Animal Sciences, College of Tropical Agriculture and Human Resources, University of Hawaii)
  • Received : 2020.05.20
  • Accepted : 2020.07.16
  • Published : 2020.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

Vitamin D insufficiency is associated with obesity and its related metabolic diseases. Adipose tissues store and metabolize vitamin D and expression levels of vitamin D metabolizing enzymes are known to be altered in obesity. Sequestration of vitamin D in large amount of adipose tissues and low vitamin D metabolism may contribute to the vitamin D inadequacy in obesity. Vitamin D receptor is expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including adipogenesis as well as metabolic and endocrine function of adipose tissues that can contribute to the high risk of metabolic diseases in vitamin D insufficiency. We will review current understanding of vitamin D regulation of adipose biology focusing on vitamin D modulation of adiposity and adipose tissue functions as well as the molecular mechanisms through which vitamin D regulates adipose biology. The effects of supplementation or maintenance of vitamin D on obesity and metabolic diseases are also discussed.

Keywords

References

  1. Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest 2017;127:74-82. https://doi.org/10.1172/JCI88883
  2. Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med 2013;34:1-11. https://doi.org/10.1016/j.mam.2012.10.001
  3. Shabalina IG, Petrovic N, de Jong JM, Kalinovich AV, Cannon B, Nedergaard J. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Reports 2013;5:1196-203. https://doi.org/10.1016/j.celrep.2013.10.044
  4. Yoneshiro T, Saito M. Activation and recruitment of brown adipose tissue as anti-obesity regimens in humans. Ann Med 2015;47:133-41. https://doi.org/10.3109/07853890.2014.911595
  5. Umar M, Sastry KS, Chouchane AI. Role of vitamin D beyond the skeletal function: a review of the molecular and clinical studies. Int J Mol Sci 2018;19:1618. https://doi.org/10.3390/ijms19061618
  6. Mutt SJ, Hypponen E, Saarnio J, Jarvelin MR, Herzig KH. Vitamin D and adipose tissue-more than storage. Front Physiol 2014;5:228.
  7. Thacher TD, Levine MA. CYP2R1 mutations causing vitamin D-deficiency rickets. J Steroid Biochem Mol Biol 2017;173:333-6. https://doi.org/10.1016/j.jsbmb.2016.07.014
  8. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev 2019;40:1109-51. https://doi.org/10.1210/er.2018-00126
  9. Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 2012;441:61-76. https://doi.org/10.1042/BJ20110744
  10. Sun X, Zemel MB. Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity (Silver Spring) 2007;15:340-8. https://doi.org/10.1038/oby.2007.540
  11. Hii CS, Ferrante A. The non-genomic actions of vitamin D. Nutrients 2016;8:135. https://doi.org/10.3390/nu8030135
  12. Silvagno F, Consiglio M, Foglizzo V, Destefanis M, Pescarmona G. Mitochondrial translocation of vitamin D receptor is mediated by the permeability transition pore in human keratinocyte cell line. PLoS One 2013;8:e54716. https://doi.org/10.1371/journal.pone.0054716
  13. Silvagno F, Pescarmona G. Spotlight on vitamin D receptor, lipid metabolism and mitochondria: Some preliminary emerging issues. Mol Cell Endocrinol 2017;450:24-31. https://doi.org/10.1016/j.mce.2017.04.013
  14. Rosenstreich SJ, Rich C, Volwiler W. Deposition in and release of vitamin $D_{3}$ from body fat: evidence for a storage site in the rat. J Clin Invest 1971;50:679-87. https://doi.org/10.1172/JCI106538
  15. Nimitphong H, Holick MF, Fried SK, Lee MJ. 25-hydroxyvitamin $D_{3}$ and 1,25-dihydroxyvitamin $D_{3}$ promote the differentiation of human subcutaneous preadipocytes. PLoS One 2012;7:e52171. https://doi.org/10.1371/journal.pone.0052171
  16. Wamberg L, Christiansen T, Paulsen SK, Fisker S, Rask P, Rejnmark L, Richelsen B, Pedersen SB. Expression of vitamin D-metabolizing enzymes in human adipose tissue -- the effect of obesity and diet-induced weight loss. Int J Obes 2013;37:651-7. https://doi.org/10.1038/ijo.2012.112
  17. Clemente-Postigo M, Munoz-Garach A, Serrano M, Garrido-Sanchez L, Bernal-Lopez MR, Fernandez-Garcia D, Moreno-Santos I, Garriga N, Castellano-Castillo D, Camargo A, Fernandez-Real JM, Cardona F, Tinahones FJ, Macias-Gonzalez M. 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.
  18. Nguyen VT, Li X, Elli EF, Ayloo SM, Castellanos KJ, Fantuzzi G, Freels S, Braunschweig CL. Vitamin D, inflammation, and relations to insulin resistance in premenopausal women with morbid obesity. Obesity (Silver Spring) 2015;23:1591-7. https://doi.org/10.1002/oby.21131
  19. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P. Dynamics of fat cell turnover in humans. Nature 2008;453:783-7. https://doi.org/10.1038/nature06902
  20. Lee MJ, Wu Y, Fried SK. Adipose tissue remodeling in pathophysiology of obesity. Curr Opin Clin Nutr Metab Care 2010;13:371-6. https://doi.org/10.1097/MCO.0b013e32833aabef
  21. Gustafson B, Hedjazifar S, Gogg S, Hammarstedt A, Smith U. Insulin resistance and impaired adipogenesis. Trends Endocrinol Metab 2015;26:193-200. https://doi.org/10.1016/j.tem.2015.01.006
  22. Lee MJ, Pickering RT, Shibad V, Wu Y, Karastergiou K, Jager M, Layne MD, Fried SK. Impaired glucocorticoid suppression of TGF${\beta}$ signaling in human omental adipose tissues limits adipogenesis and may promote fibrosis. Diabetes 2019;68:587-97. https://doi.org/10.2337/db18-0955
  23. Lee MJ. Hormonal regulation of adipogenesis. Compr Physiol 2017;7:1151-95.
  24. Blumberg JM, Tzameli I, Astapova I, Lam FS, Flier JS, Hollenberg AN. Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells. J Biol Chem 2006;281:11205-13. https://doi.org/10.1074/jbc.M510343200
  25. Kong J, Li YC. Molecular mechanism of 1,25-dihydroxyvitamin $D_{3}$ inhibition of adipogenesis in 3T3-L1 cells. Am J Physiol Endocrinol Metab 2006;290:E916-24. https://doi.org/10.1152/ajpendo.00410.2005
  26. Narvaez CJ, Simmons KM, Brunton J, Salinero A, Chittur SV, Welsh JE. Induction of STEAP4 correlates with 1,25-dihydroxyvitamin $D_{3}$ stimulation of adipogenesis in mesenchymal progenitor cells derived from human adipose tissue. J Cell Physiol 2013;228:2024-36. https://doi.org/10.1002/jcp.24371
  27. Felicidade I, Sartori D, Coort SL, Semprebon SC, Niwa AM, D'Epiro GF, Biazi BI, Marques LA, Evelo CT, Mantovani MS, Ribeiro LR. Role of $1{\alpha}$,25-dihydroxyvitamin $D_{3}$ in adipogenesis of SGBS cells: new insights into human preadipocyte proliferation. Cell Physiol Biochem 2018;48:397-408.
  28. Mahajan A, Stahl CH. Dihydroxy-cholecalciferol stimulates adipocytic differentiation of porcine mesenchymal stem cells. J Nutr Biochem 2009;20:512-20. https://doi.org/10.1016/j.jnutbio.2008.05.010
  29. Nobre JL, Lisboa PC, Carvalho JC, Martins MR, Vargas S, Barja-Fidalgo C, de Moura EG, de Oliveira E. Leptin blocks the inhibitory effect of vitamin D on adipogenesis and cell proliferation in 3T3-L1 adipocytes. Gen Comp Endocrinol 2018;266:1-8. https://doi.org/10.1016/j.ygcen.2018.01.014
  30. Shi H, Norman AW, Okamura WH, Sen A, Zemel MB. $1{\alpha}$,25-Dihydroxyvitamin $D_{3}$ modulates human adipocyte metabolism via nongenomic action. FASEB J 2001;15:2751-3.
  31. Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, Sun XJ, Li YC. Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. Am J Physiol Endocrinol Metab 2009;296:E820-8. https://doi.org/10.1152/ajpendo.90763.2008
  32. Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J. Lean phenotype and resistance to diet-induced obesity in vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue. Endocrinology 2009;150:651-61. https://doi.org/10.1210/en.2008-1118
  33. Matthews DG, D'Angelo J, Drelich J, Welsh J. Adipose-specific VDR deletion alters body fat and enhances mammary epithelial density. J Steroid Biochem Mol Biol 2016;164:299-308. https://doi.org/10.1016/j.jsbmb.2015.09.035
  34. Wong KE, Kong J, Zhang W, Szeto FL, Ye H, Deb DK, Brady MJ, Li YC. Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J Biol Chem 2011;286:33804-10. https://doi.org/10.1074/jbc.M111.257568
  35. Schutkowski A, Max D, Bonn M, Brandsch C, Grundmann SM, Hirche F, Staege MS, Stangl GI. Vitamin D does not play a functional role in adipose tissue development in rodent models. Mol Nutr Food Res 2018;62:62.
  36. Belenchia AM, Jones KL, Will M, Beversdorf DQ, Vieira-Potter V, Rosenfeld CS, Peterson CA. Maternal vitamin D deficiency during pregnancy affects expression of adipogenic-regulating genes peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and vitamin D receptor (VDR) in lean male mice offspring. Eur J Nutr 2018;57:723-30. https://doi.org/10.1007/s00394-016-1359-x
  37. Chang E, Kim Y. Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes. Nutrition 2016;32:702-8. https://doi.org/10.1016/j.nut.2015.12.032
  38. Larrick BM, Kim KH, Donkin SS, Teegarden D. 1,25-Dihydroxyvitamin D regulates lipid metabolism and glucose utilization in differentiated 3T3-L1 adipocytes. Nutr Res 2018;58:72-83. https://doi.org/10.1016/j.nutres.2018.07.004
  39. Bhat M, Noolu B, Qadri SS, Ismail A. Vitamin D deficiency decreases adiposity in rats and causes altered expression of uncoupling proteins and steroid receptor coactivator3. J Steroid Biochem Mol Biol 2014;144 Pt B:304-12. https://doi.org/10.1016/j.jsbmb.2014.08.005
  40. Marcotorchino J, Gouranton E, Romier B, Tourniaire F, Astier J, Malezet C, Amiot MJ, Landrier JF. Vitamin D reduces the inflammatory response and restores glucose uptake in adipocytes. Mol Nutr Food Res 2012;56:1771-82. https://doi.org/10.1002/mnfr.201200383
  41. Manna P, Jain SK. Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-${\gamma}$-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. J Biol Chem 2012;287:42324-32. https://doi.org/10.1074/jbc.M112.407833
  42. Manna P, Achari AE, Jain SK. Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys 2017;615:22-34. https://doi.org/10.1016/j.abb.2017.01.002
  43. Sun X, Morris KL, Zemel MB. Role of calcitriol and cortisol on human adipocyte proliferation and oxidative and inflammatory stress: a microarray study. J Nutrigenet Nutrigenomics 2008;1:30-48. https://doi.org/10.1159/000109873
  44. Lorente-Cebrian S, Eriksson A, Dunlop T, Mejhert N, Dahlman I, Astrom G, Sjolin E, Wahlen K, Carlberg C, Laurencikiene J, Heden P, Arner P, Ryden M. Differential effects of $1{\alpha}$,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes. Eur J Nutr 2012;51:335-42. https://doi.org/10.1007/s00394-011-0218-z
  45. Wamberg L, Cullberg KB, Rejnmark L, Richelsen B, Pedersen SB. Investigations of the anti-inflammatory effects of vitamin D in adipose tissue: results from an in vitro study and a randomized controlled trial. Horm Metab Res 2013;45:456-62. https://doi.org/10.1055/s-0032-1331746
  46. Ding C, Wilding JP, Bing C. 1,25-Dihydroxyvitamin $D_{3}$ protects against macrophage-induced activation of $NF{\kappa}B$ and MAPK signalling and chemokine release in human adipocytes. PLoS One 2013;8:e61707. https://doi.org/10.1371/journal.pone.0061707
  47. Gao D, Trayhurn P, Bing C. 1,25-Dihydroxyvitamin $NF{\kappa}B$ inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int J Obes 2013;37:357-65. https://doi.org/10.1038/ijo.2012.53
  48. Karkeni E, Marcotorchino J, Tourniaire F, Astier J, Peiretti F, Darmon P, Landrier JF. Vitamin D limits chemokine expression in adipocytes and macrophage migration in vitro and in male mice. Endocrinology 2015;156:1782-93. https://doi.org/10.1210/en.2014-1647
  49. Kaneko I, Sabir MS, Dussik CM, Whitfield GK, Karrys A, Hsieh JC, Haussler MR, Meyer MB, Pike JW, Jurutka PW. 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J 2015;29:4023-35. https://doi.org/10.1096/fj.14-269811
  50. Kong J, Chen Y, Zhu G, Zhao Q, Li YC. 1,25-Dihydroxyvitamin $NF{\kappa}B$ upregulates leptin expression in mouse adipose tissue. J Endocrinol 2013;216:265-71. https://doi.org/10.1530/JOE-12-0344
  51. Sun J, Kong J, Duan Y, Szeto FL, Liao A, Madara JL, Li YC. Increased $NF-{\kappa}B$ activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 2006;291:E315-22. https://doi.org/10.1152/ajpendo.00590.2005
  52. Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 2012;188:2127-35. https://doi.org/10.4049/jimmunol.1102412
  53. Chun RF, Lauridsen AL, Suon L, Zella LA, Pike JW, Modlin RL, Martineau AR, Wilkinson RJ, Adams J, Hewison M. Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 2010;95:3368-76. https://doi.org/10.1210/jc.2010-0195
  54. Christakos S, Dhawan P, Ajibade D, Benn BS, Feng J, Joshi SS. Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D. J Steroid Biochem Mol Biol 2010;121:183-7. https://doi.org/10.1016/j.jsbmb.2010.03.005
  55. Jamka M, Wozniewicz M, Walkowiak J, Bogdanski P, Jeszka J, Stelmach-Mardas M. The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis. Eur J Nutr 2016;55:2163-76. https://doi.org/10.1007/s00394-015-1089-5
  56. Dinca M, Serban MC, Sahebkar A, Mikhailidis DP, Toth PP, Martin SS, Blaha MJ, Bluher M, Gurban C, Penson P, Michos ED, Hernandez AV, Jones SR, Banach M; Lipid Blood Pressure Meta-analysis Collaboration LBPMC Group. Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2016;107:360-71. https://doi.org/10.1016/j.phrs.2016.03.035
  57. Hajimohammadi M, Shab-Bidar S, Neyestani TR. Vitamin D and serum leptin: a systematic review and meta-analysis of observational studies and randomized controlled trials. Eur J Clin Nutr 2017;71:1144-53. https://doi.org/10.1038/ejcn.2016.245
  58. Yu Y, Tian L, Xiao Y, Huang G, Zhang M. Effect of vitamin D supplementation on some inflammatory biomarkers in type 2 diabetes mellitus subjects: a systematic review and meta-analysis of randomized controlled trials. Ann Nutr Metab 2018;73:62-73. https://doi.org/10.1159/000490358
  59. Romagnoli E, Pepe J, Piemonte S, Cipriani C, Minisola S. Management of endocrine disease: value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation. Eur J Endocrinol 2013;169:R59-69. https://doi.org/10.1530/EJE-13-0435
  60. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011;96:53-8. https://doi.org/10.1210/jc.2010-2704
  61. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R; National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25:2359-81. https://doi.org/10.1007/s00198-014-2794-2
  62. Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, Burckhardt P, Fuleihan GE, Josse RG, Lips P, Morales-Torres J, Yoshimura N. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int 2010;21:1151-4. https://doi.org/10.1007/s00198-010-1285-3
  63. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF; Elizabeth Glaser Pediatric Research Network Obesity Study Group. Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr 2009;90:459-67. https://doi.org/10.3945/ajcn.2008.27275
  64. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004. Am J Clin Nutr 2008;88:1519-27. https://doi.org/10.3945/ajcn.2008.26182
  65. Valina-Toth AL, Lai Z, Yoo W, Abou-Samra A, Gadegbeku CA, Flack JM. Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans. Clin Endocrinol (Oxf) 2010;72:595-603. https://doi.org/10.1111/j.1365-2265.2009.03676.x
  66. 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. https://doi.org/10.1093/ajcn/72.3.690
  67. 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. https://doi.org/10.1038/oby.2011.404
  68. Pathak K, Soares MJ, Calton EK, Zhao Y, Hallett J. Vitamin D supplementation and body weight status: a systematic review and meta-analysis of randomized controlled trials. Obes Rev 2014;15:528-37. https://doi.org/10.1111/obr.12162
  69. Chandler PD, Wang L, Zhang X, Sesso HD, Moorthy MV, Obi O, Lewis J, Prince RL, Danik JS, Manson JE, LeBoff MS, Song Y. Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 2015;73:577-93. https://doi.org/10.1093/nutrit/nuv012
  70. Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, LeBoff MS, Margolis KL, Powell L, Uwaifo G, Whitlock E, Wylie-Rosett J, LaCroix A. Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. Arch Intern Med 2007;167:893-902. https://doi.org/10.1001/archinte.167.9.893
  71. Tuomainen TP, Virtanen JK, Voutilainen S, Nurmi T, Mursu J, de Mello VD, Schwab U, Hakumaki M, Pulkki K, Uusitupa M. Glucose metabolism effects of vitamin D in prediabetes: the VitDmet randomized placebo-controlled supplementation study. J Diabetes Res 2015;2015:672653. https://doi.org/10.1155/2015/672653
  72. Mitchell DM, Leder BZ, Cagliero E, Mendoza N, Henao MP, Hayden DL, Finkelstein JS, Burnett-Bowie SA. Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. Am J Clin Nutr 2015;102:385-92. https://doi.org/10.3945/ajcn.115.111682
  73. Cassity EP, Redzic M, Teager CR, Thomas DT. The effect of body composition and BMI on 25(OH)D response in vitamin D-supplemented athletes. Eur J Sport Sci 2016;16:773-9. https://doi.org/10.1080/17461391.2015.1125952
  74. Sadiya A, Ahmed SM, Carlsson M, Tesfa Y, George M, Ali SH, Siddieg HH, Abusnana S. Vitamin $D_{3}$ supplementation and body composition in persons with obesity and type 2 diabetes in the UAE: A randomized controlled double-blinded clinical trial. Clin Nutr 2016;35:77-82. https://doi.org/10.1016/j.clnu.2015.02.017
  75. Mousa A, Naderpoor N, de Courten MP, Teede H, Kellow N, Walker K, Scragg R, de Courten B. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial. Am J Clin Nutr 2017;105:1372-81. https://doi.org/10.3945/ajcn.117.152736
  76. Karefylakis C, Sarnblad S, Ariander A, Ehlersson G, Rask E, Rask P. Effect of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men-a randomized controlled trial. Endocrine 2018;61:388-97. https://doi.org/10.1007/s12020-018-1665-6
  77. Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaelsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, Salomaa V, Campbell H, Dunlop M, Mitchell BD, Herzig KH, Pouta A, Hartikainen AL, Streeten EA, Theodoratou E, Jula A, Wareham NJ, Ohlsson C, Frayling TM, Kritchevsky SB, Spector TD, Richards JB, Lehtimaki T, Ouwehand WH, Kraft P, Cooper C, Marz W, Power C, Loos RJ, Wang TJ, Jarvelin MR, Whittaker JC, Hingorani AD, Hypponen E. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med 2013;10:e1001383. https://doi.org/10.1371/journal.pmed.1001383
  78. Jamka M, Wozniewicz M, Jeszka J, Mardas M, Bogdanski P, Stelmach-Mardas M. The effect of vitamin D supplementation on insulin and glucose metabolism in overweight and obese individuals: systematic review with meta-analysis. Sci Rep 2015;5:16142. https://doi.org/10.1038/srep16142
  79. Rejnmark L, Bislev LS, Cashman KD, Eiriksdottir G, Gaksch M, Grubler M, Grimnes G, Gudnason V, Lips P, Pilz S, van Schoor NM, Kiely M, Jorde R. Non-skeletal health effects of vitamin D supplementation: a systematic review on findings from meta-analyses summarizing trial data. PLoS One 2017;12:e0180512. https://doi.org/10.1371/journal.pone.0180512
  80. Mirhosseini N, Vatanparast H, Mazidi M, Kimball SM. The effect of improved serum 25-hydroxyvitamin D status on glycemic control in diabetic patients: a meta-analysis. J Clin Endocrinol Metab 2017;102:3097-110. https://doi.org/10.1210/jc.2017-01024
  81. Asemi Z, Foroozanfard F, Hashemi T, Bahmani F, Jamilian M, Esmaillzadeh A. Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome. Clin Nutr 2015;34:586-92. https://doi.org/10.1016/j.clnu.2014.09.015

Cited by

  1. Vitamin D Status and Its Correlation With Anthropometric and Biochemical Indicators of Cardiometabolic Risk in Serbian Underground Coal Miners in 2016 vol.8, 2021, https://doi.org/10.3389/fnut.2021.689214
  2. Vitamin D Status and Its Influence on the Health of Preschool Children in Hangzhou vol.9, 2020, https://doi.org/10.3389/fpubh.2021.675403
  3. Salt Intake, Aldosterone Secretion, and Obesity: Role in the Pathogenesis of Resistant Hypertension vol.34, pp.6, 2020, https://doi.org/10.1093/ajh/hpab015
  4. Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide vol.13, pp.14, 2020, https://doi.org/10.3390/cancers13143577
  5. Lower Levels of Vitamin D Are Associated with an Increase in Insulin Resistance in Obese Brazilian Women vol.13, pp.9, 2021, https://doi.org/10.3390/nu13092979