Abstract

The presence of vitamin D receptors in β-cells, in the cells of intestine, skeletal system, lungs, lymphocytes, monocytes and adipocytes indicates its multidirectional activity. Vitamin D has the ability to modify the process of adipogenesis by inducing transcription factors and affecting the remodeling of adipose tissue. Due to the presence of specific receptors in adipocytes, vitamin D affects the systemic regulation of energy homeostasis. Vitamin D receptor knockout mice have lower body weight and better tolerance to high-energy diets, whereas the overexpression of this receptor leads to the occurrence of obesity. Vitamin D inhibits or stimulates the synthesis of adipokines (leptin, resistin, adiponectin), although research in this field is inconclusive. Vitamin D reduces inflammation mainly by decreasing the production of proinflammatory cytokines. It has also been indicated that adipose tissue affects the metabolism of vitamin D. Preadipocytes and mature adipocytes modulate the activity of enzymes involved in the hydroxylation and metabolism of this vitamin. Vitamin D binding protein also plays an important role, as, in addition to controlling the metabolism of this compound, it may participate in the pathogenesis of complications of obesity. Vitamin D deficiencies in various niejedpopulation groups, particularly in people with excess adipose tissue, lead to many metabolic dysfunctions, such as carbohydrate and lipid disorders. Thus, the proper supply of this vitamin is important for improving health condition. The aim of the study is to review the data on the effects of vitamin D on the process of adipogenesis and adipocyte role in the metabolism of this vitamin, its impact on energy homeostasis, adipokines synthesis and inflammatory reactions.

References

• 1. Ashraf A.P., Huisingh C., Alvarez J.A., Wang X., Gower B.A.: Insulin resistance indices are inversely associated with vitamin D binding protein concentrations. J. Clin. Endocrinol. Metab., 2014; 99: 178-183
  Google Scholar
• 2. Baziar N., Jafarian K., Shadman Z., Qorbani M., Khoshniat Nikoo M., Abd Mishani M.: Effect of therapeutic dose of vitamin D on serum adiponectin and glycemia in vitamin D-insufficient or deficient type 2 diabetic patients. Iran. Red Crescent Med. J., 2014; 16: e21458
  Google Scholar
• 3. Bikle D.D: Extra renal synthesis of 1,25-dihydroxyvitamin D and its health implications. Clin. Rev. Bone Mineral Metab., 2009; 7: 114- 125
  Google Scholar
• 4. Blum M., Dolnikowski G., Seyoum E., Harris S.S., Booth S.L., Peterson J., Saltzman E., Dawson-Hughes B.: Vitamin D3 in fat tissue. Endocrine, 2008; 33: 90-94
  Google Scholar
• 5. Blumberg J.M., Tzameli I., Astapova I., Lam F.S., Flier J.S., Hollenberg A.N.: Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells. J. Biol. Chem., 2006; 281: 11205-11213
  Google Scholar
• 6. Bouillon R., Carmeliet G., Lieben L., Watanabe M., Perino A., Auwerx J., Schoonjans K., Verstuyf A.: Vitamin D and energy homeostasis of mice and men. Nat. Rev. Endocrinol., 2014; 10: 79-87
  Google Scholar
• 7. Cantorna M.T., Mahon B.D.: D-hormone and the immune system. J. Rheumatol. Suppl., 2005; 76: 11-20
  Google Scholar
• 8. Ching S., Kashinkunti S., Niehaus M.D., Zinser G.M.: Mammary adipocytes bioactivate 25-hydroxyvitamin D3 and signal via vitamin D3 receptor, modulating mammary epithelial cell growth. J. Cell. Biochem., 2011; 112: 3393-3405
  Google Scholar
• 9. Chun R.F.: New perspectives on the vitamin D binding protein. Cell Biochem. Funct., 2012; 30: 445-456
  Google Scholar
• 10. Cipriani C., Pepe J., Piemonte S., Colangelo L., Cilli M., Minisola S.: Vitamin D and its relationship with obesity and muscle. Int. J. Endocrinol., 2014; 2014: 841248
  Google Scholar
• 11. Ding C., Gao D., Wilding J., Trayhurn P., Bing C.: Vitamin D signalling in adipose tissue. Br. J. Nutr., 2012; 108: 1915-1923
  Google Scholar
• 12. Ding C., Wilding J.P., Bing C.: 1,25-dihydroxyvitamin D3 protects against macrophage-induced activation of NFκB and MAPK signalling and chemokine release in human adipocytes. PLoS One, 2013; 8: e61707
  Google Scholar
• 13. Ellulu M., Abed Y., Rahmat A., Ranneh Y., Ali F.: Epidemiology of obesity in developing countries: challenges and prevention. Global Epidemic Obesity, 2014; 2: 2
  Google Scholar
• 14. Fraser W.D., Milan A.M.: Vitamin D assays: past and present debates, difficulties, and developments. Calcif. Tissue Int., 2013; 92: 118-127
  Google Scholar
• 15. Fu M., Sun T., Bookout A.L., Downes M., Yu R.T., Evans R.M., Mangelsdorf D.J.: A nuclear receptor atlas: 3T3-L1 adipogenesis. Mol. Endocrinol., 2005; 19: 2437-2450
  Google Scholar
• 16. Galic S., Oakhill J.S., Steinberg G.R.: Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol., 2010; 316: 129-139
  Google Scholar
• 17. Gao D., Trayhurn P., Bing C.: 1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int. J. Obes., 2013; 37: 357-365
  Google Scholar
• 18. Giulietti A., van Etten E., Overbergh L., Stoffels K., Bouillon R., Mathieu C.: Monocytes from type 2 diabetic patients have a proinflammatory profile. 1,25-Dihydroxyvitamin D3 works as anti-inflammatory. Diabetes Res. Clin. Pract., 2007; 77: 47-57
  Google Scholar
• 19. González-Molero I., Rojo-Martínez G., Morcillo S., Gutierrez C., Rubio E., Pérez-Valero V., Esteva I., Ruiz de Adana M.S., Almaraz M.C., Colomo N., Olveira G., Soriguer F.: Hypovitaminosis D and incidence of obesity: a prospective study. Eur. J. Clin. Nutr., 2013; 67: 680-682
  Google Scholar
• 20. Goossens G.H.: The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav., 2008; 94: 206-218
  Google Scholar
• 21. Gruber B.M.: Fenomen witaminy D. Postępy Hig. Med. Dośw., 2015; 69: 127-139
  Google Scholar
• 22. Husemoen L.L., Skaaby T., Martinussen T., Jørgensen T., Thuesen B.H., Kistorp C., Jeppesen J., Thyssen J.P., Meldgaard M., Szecsi P.B., Fenger M., Linneberg A.: Investigating the causal effect of vitamin D on serum adiponectin using a Mendelian randomization approach. Eur. J. Clin. Nutr., 2014; 68: 189-195
  Google Scholar
• 23. Keisala T., Minasyan A., Lou Y.R., Zou J., Kalueff A.V., Pyykkö I., Tuohimaa P.: Premature aging in vitamin D receptor mutant mice. J. Steroid Biochem. Mol. Biol., 2009; 115: 91-97
  Google Scholar
• 24. Kong J., Chen Y., Zhu G., Zhao Q., Li Y.C.: 1,25-dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. J. Endocrinol., 2013; 216: 265-271
  Google Scholar
• 25. Kong J., Li Y.C.: Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am. J. Physiol. Endocrinol. Metab., 2006; 290: E916-E924
  Google Scholar
• 26. Koszowska A.U., Nowak J., Dittfeld A., Brończyk-Puzoń A., Kulpok A., Zubelewicz-Szkodzińska B.: Obesity, adipose tissue function and the role of vitamin D. Cent. Eur. J. Immunol., 2014; 39: 260-264
  Google Scholar
• 27. Li J., Byrne M.E., Chang E., Jiang Y., Donkin S.S., Buhman K.K., Burgess J.R., Teegarden D.: 1α,25-Dihydroxyvitamin D hydroxylase in adipocytes. J. Steroid Biochem. Mol. Biol., 2008; 112: 122-126
  Google Scholar
• 28. Lolmède K., Duffaut C., Zakaroff-Girard A., Bouloumié A.: Immune cells in adipose tissue: Key players in metabolic disorders. Diabetes Metab., 2011, 37: 283-290
  Google Scholar
• 29. Lorente-Cebrián S., Eriksson A., Dunlop T., Mejhert N., Dahlman I., Aström G., Sjölin E., Wåhlén K., Carlberg C., Laurencikiene J., Hedén P., Arner P., Rydén M.: Differential effects of 1α,25- dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes. Eur. J. Nutr., 2012, 51: 335-342
  Google Scholar
• 30. Luong K.V., Nguyen L.T.: The beneficial role of vitamin D in obesity: possible genetic and cell signaling mechanisms. Nutr. J., 2013; 12: 89
  Google Scholar
• 31. Luong K.V., Nguyen L.T.: Vitamin D and obesity. Med. Chem., 2012; 2: 011-019
  Google Scholar
• 32. Łukaszewicz-Zając M., Mroczko B., Kułakowska A., Szmitkowski M.: Znaczenie Gc-globuliny w praktyce klinicznej. Postępy Hig. Med. Dośw., 2008; 62: 625-631
  Google Scholar
• 33. Marcotorchino J., Gouranton E., Romier B., Tourniaire F., Astier J., Malezet C., Amiot M.J., Landrier J.F.: Vitamin D reduces the inflammatory response and restores glucose uptake in adipocytes. Mol. Nutr. Food Res., 2012; 56: 1771-1782
  Google Scholar
• 34. Menendez C., Lage M., Peino R., Baldelli R., Concheiro P., Diéguez C., Casanueva F.F.: Retinoic acid and vitamin D3 powerfully inhibit in vitro leptin secretion by human adipose tissue. J. Endocrinol., 2001; 170: 425-431
  Google Scholar
• 35. Mozos I., Marginean O. Links between vitamin D deficiency and cardiovascular diseases. Biomed. Res. Int., 2015; 2015: 109275
  Google Scholar
• 36. Mutt S.J., Hyppönen E., Saarnio J., Järvelin M.R., Herzig K.H.: Vitamin D and adipose tissue – more than storage. Front. Physiol., 2014; 5: 228
  Google Scholar
• 37. Mutt S.J., Karhu T., Lehtonen S., Lehenkari P., Carlberg C., Saarnio J., Sebert S., Hyppönen E., Järvelin M.R., Herzig K.H.: Inhibition of cytokine secretion from adipocytes by 1,25-dihydroxyvitamin D₃ via the NF-κB pathway. FASEB J., 2012; 26: 4400-4407
  Google Scholar
• 38. Narvaez C.J., 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: 651-661
  Google Scholar
• 39. Nimitphong H., Holick M.F., Fried S.K., Lee M.J.: 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 promote the differentiation of human subcutaneous preadipocytes. PLoS One, 2012; 7: e52171
  Google Scholar
• 40. O’Hara A., Lim F.L., Mazzatti D.J., Trayhurn P.: Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is up-regulated in human adipocytes by macrophageconditioned medium. Pflugers Arch., 2009; 458: 1103-1114
  Google Scholar
• 41. Peluso I., Palmery M.: The relationship between body weight and inflammation: Lesson from anti-TNF-α antibody therapy. Hum. Immunol., 2016; 77: 47-53
  Google Scholar
• 42. Pełczyńska M., Jaroszewicz I., Świtalska M., Opolski A.: Właściwości biologiczne kalcytriolu i jego nowych analogów – potencjalne zastosowania terapeutyczne. Postępy Hig. Med. Dośw., 2005; 59: 129-139
  Google Scholar
• 43. Prasad P., Kochhar A.: Interplay of vitamin D and metabolic syndrome: a review. Diabetes Metab. Syndr., 2016; 10: 105-112
  Google Scholar
• 44. Rezaee F., Dashty M.: Role of adipose tissue in metabolic system disorders – adipose tissue is the initiator of metabolic diseases. J. Diabetes Metab., 2013; S13: 008
  Google Scholar
• 45. Safadi F.F., Thornton P., Magiera H., Hollis B.W., Gentile M., Haddad J.G., Liebhaber S.A., Cooke N.E.: Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J. Clin. Invest., 1999; 103: 239-251
  Google Scholar
• 46. Sergeev I.N.: 1,25-dihydroxyvitamin D3 induces Ca2+-mediated apoptosis in adipocytes via activation of calpain and caspase-12. Biochem. Biophys. Res. Commun., 2009; 384: 18-21
  Google Scholar
• 47. Song Q., Sergeev I.N.: Calcium and vitamin D in obesity. Nutr. Res. Rev., 2012; 25: 130-141
  Google Scholar
• 48. Speeckaert M., Huang G., Delanghe J.R., Taes Y.E.: Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin. Chim. Acta, 2006; 372: 33-42
  Google Scholar
• 49. Speeckaert M.M., Taes Y.E., De Buyzere M.L., Christophe A.B., Kaufman J.M., Delanghe J.R.: Investigation of the potential association of vitamin D binding protein with lipoproteins. Ann. Clin. Biochem., 2010; 47: 143-150
  Google Scholar
• 50. Stokić E., Kupusinac A., Tomic-Naglic D., Smiljenic D., KovacevZavisic B., Srdic-Galic B., Soskic S., Isenovic E.R.: Vitamin D and dysfunctional adipose tissue in obesity. Angiology, 2015; 66: 613-618
  Google Scholar
• 51. Strange R.C., Shipman K.E., Ramachandran S.: Metabolic syndrome: a review of the role of vitamin D in mediating susceptibility and outcome. World J. Diabetes, 2015; 6: 896-911
  Google Scholar
• 52. Sun X., Zemel M.B.: Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity, 2007; 15: 340-348
  Google Scholar
• 53. Tabesh M., Azadbakht L., Faghihimani E., Tabesh M., Esmaillzadeh A.: Calcium-vitamin D cosupplementation influences circulating inflammatory biomarkers and adipocytokines in vitamin Dinsufficient diabetics: a randomized controlled clinical trial. J. Clin. Endocrinol. Metab., 2014; 99: E2485-E2493
  Google Scholar
• 54. Tourniaire F., Romier-Crouzet B., Lee J.H., Marcotorchino J., Gouranton E., Salles J., Malezet C., Astier J., Darmon P., Blouin E., Walrand S., Ye J., Landrier J.F.: Chemokine expression in inflamed adipose tissue is mainly mediated by NF-κB. PLoS One, 2013; 8: e66515
  Google Scholar
• 55. Trayhurn P.: Hypoxia and adipose tissue function and dysfunction in obesity. Physiol. Rev., 2013; 93: 1-21
  Google Scholar
• 56. Trayhurn P., O’Hara A., Bing C.: Interrogation of microarray datasets indicates that macrophage-secreted factors stimulate the expression of genes associated with vitamin D metabolism (VDR and CYP27B1) in human adipocytes. Adipobiology, 2011; 3: 29-34
  Google Scholar
• 57. Tukaj C.: Właściwy poziom witaminy D warunkiem zachowania zdrowia. Postępy Hig. Med. Dośw., 2008; 62: 502-510
  Google Scholar
• 58. Tuohimaa P.: Vitamin D and aging. J. Steroid Biochem. Mol. Biol., 2009; 114, 78-84
  Google Scholar
• 59. Vanlint S.: Vitamin D and obesity. Nutrients, 2013; 5: 949-956
  Google Scholar
• 60. Vilarrasa N., Vendrell J., Maravall J., Elío I., Solano E., San José P., García I., Virgili N., Soler J., Gómez J.M.: Is plasma 25(OH) D related to adipokines, inflammatory cytokines and insulin resistance in both a healthy and morbidly obese population? Endocrine, 2010; 38: 235-242
  Google Scholar
• 61. Walker G.E., Marzullo P., Ricotti R., Bona G., Prodam F.: The pathophysiology of abdominal adipose tissue depots in health and disease. Horm. Mol. Biol. Clin. Investig., 2014; 19: 57-74
  Google Scholar
• 62. Wamberg L., Christiansen T., Paulsen S.K., Fisker S., Rask P., Rejnmark L., Richelsen B., Pedersen S.B.: Expression of vitamin Dmetabolizing enzymes in human adipose tissue – the effect of obesity and diet-induced weight loss. Int. J. Obes., 2013; 37: 651-657
  Google Scholar
• 63. Wamberg L., Cullberg K.B., Rejnmark L., Richelsen B., Pedersen S.B.: 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: 456-462
  Google Scholar
• 64. Wamberg L., Pedersen S.B., 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: 429-440
  Google Scholar
• 65. Wang C.: Role of vitamin D in cardiometabolic diseases. J. Diabetes Res., 2013; 2013: 243934
  Google Scholar
• 66. Wang H., Ye J.: Regulation of energy balance by inflammation: common theme in physiology and pathology. Rev. Endocr. Metab. Disord., 2015; 16: 47-54
  Google Scholar
• 67. Weber K., Erben R.G.: Differences in triglyceride and cholesterol metabolism and resistance to obesity in male and female vitamin D receptor knockout mice. J. Anim. Physiol. Anim. Nutr., 2013; 97: 675-683
  Google Scholar
• 68. Weinstein S.J., Stolzenberg-Solomon R.Z., Kopp W., Rager H., Virtamo J., Albanes D.: Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin D and pancreatic cancer risk: a nested case-control study. Cancer Res., 2012; 72: 1190-1198
  Google Scholar
• 69. Wong K.E., Kong J., Zhang W., Szeto F.L., Ye H., Deb D.K., Brady M.J., Li Y.C.: Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J. Biol. Chem., 2011; 286: 33804-33810
  Google Scholar
• 70. Wong K.E., Szeto F.L., Zhang W., Ye H., Kong J., Zhang Z., Sun X.J., Li Y.C.: Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. Am. J. Physiol. Endocrinol. Metab., 2009; 296: E820-E828
  Google Scholar
• 71. Wright O.R., Hickman I.J., Petchey W.G., Sullivan C.M., Ong C., Rose F.J., Ng C., Prins J.B., Whitehead J.P., O’Moore-Sullivan T.M.: The effect of 25-hydroxyvitamin D on insulin sensitivity in obesity: is it mediated via adiponectin? Can. J. Physiol. Pharmacol., 2013; 91: 496-501
  Google Scholar
• 72. Zhang Y., Leung D.Y., Richers B.N., Liu Y., Remigio L.K., Riches D.W., Goleva E.: Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J. Immunol., 2012; 188: 2127-2135
  Google Scholar
• 73. Zhou S.S., Li D., Chen N.N., Zhou Y.: Vitamin paradox in obesity: Deficiency or excess? World J. Diabetes, 2015; 6: 1158-1167
  Google Scholar

Full text