Vitamin D Yetersizliği ve Obezite

Yıl 2018, Cilt: 58 Sayı: 2, 108 - 116, 27.12.2018

Arif Altıntaş

Öz

Bu derleme makalesinde, Vitamin D (Vit D)-obezite ilişkisinin mekanizmasına güncel bilgiler ışığında açıklık getirilmeye çalışılmıştır. Bu ilişki, yağ doku hücrelerinde (adipozit) Vit D reseptörlerinin varlığının gösterilmesi ile başlamıştır. Yağ doku leptin, adiponektin ve resistin gibi hormonları ve TNFα, IL-1β ve IL-6 ve CRP gibi birçok inflamatuar sitokin salgılar. Vit D mezodermal hücrelerin adipozitlere farklılaşması, çoğalması ve olgunlaşması sırasında aracı birçok adipogenik faktörü (adipokin) düzenler. Adipokinler, iştah ve doyma hissi, glikoz ve lipid metabolizması, kan basıncının düzenlenmesi, yangı ve bağışıklık fonksiyonlarını etkiler. Adipozitlerde antiinflamatuar yollar Vit D ile uyarılır. Vit D, yağ dokuda IkB’nin fosforilasyonunu ve NFkB’nin çekirdeğe translokasyonunu inhibe ederek iltihaplanmayı engeller. Obezitede Vit D yağ dokuda aşırı depolanır, deride vitaminin yapımı azalır ve kanda düzeyi düşer. Vit D yetersizliği adipozitlerde lipogenezi uyararak ve Ca akışını sağlayarak dokunun yağlanmasını hızlandırır. Sonuçta yağ doku iltihaplanır ve obezite gelişir. Viseral yağ doku IL, TNF-α, MCP-1 ve resistin gibi inflamatuar adipokinleri salgılayarak hipertansiyon, insulin direnci, diyabet ve Vit D’nin metabolik anormalliklerine yol açar. 

Anahtar Kelimeler

Obezite, vitamin D, vitamin D yetersizliği

Kaynakça

• 1. Adams JS, Hewison M ( 2010). Update in vitamin D. The Journal of Clinical Endocrinology and Metabolism. 95 (2):471-78.
• 2. Anonim (2015). “About Vitamin D”. University of California, Riverside. November 2011. Retrieved January 24, 2015.
• 3. Anonim (2017). Kedi ve Köpeklerde Obezite. http://www.floryahayvanhastanesi.com/pet-kutuphane/kedi-ve-kopeklerde-obezite. Erişim tarihi: 28.04.2017.
• 4. Antuna-Puente, B.; Feve, B.; Fellahi, S.; Bastard, J.P. Adipokines: The missing link between insulin resistance and obesity. Diabetes Metab. 2008, 34, 2–11.
• 5. Balistreri CR, Caruso C and Candore G (2010). The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases. Hindawi Publishing Corporation. Mediators of Inflammation. Volume 2010, Article ID 802078, 19 pages. doi:10.1155/2010/802078.
• 6. Bell N.H., Shaw S., Turner RT (1984). Evidence that 1,25-dihydroxyvitamin D3 inhibits the hepatic production of 25-hydroxyvitamin D in man. J. Clin. Invest.74: 1540–1544.
• 7. Bell TD, Demay MB, Burnett-Bowie SA (2010). The biology and pathology of vitamin D control in bone. Journal of Cellular Biochemistry. 111 (1): 7–13.
• 8. Bland IM, Guthrie-Jones A, Taylor RD, Hill J (2010). Dog Obesity: Veterinary Practices’ and Owners’ Opinions on Cause and Management Prev Vet Med 94 (3-4), 310-315.
• 9. Bouillon R, Van Cromphaut S, Carmeliet G (2003). Intestinal calcium absorption: Molecular vitamin D mediated mechanisms. Journal of Cellular Biochemistry. 88 (2): 332–339.
• 10. Canto, C.; Gerhart-Hines, Z.; Feige, J.N.; Lagouge, M.; Noriega, L.; Milne, J.C.; Elliott, P.J.; Puigserver, P.; Auwerx, J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009, 458, 1056–1060.
• 11. Canto C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr. Opin. Lipidol. 2009, 20, 98–105.
• 12. Caton PW. Kieswich J, Yaqoob MM, Holness MJ. Sugden, M.C. Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in core clock protein expression in white adipose tissue of genetically-obese db/db mice. Diabetes Obes. Metab. 2011, 13, 1097-1104.
• 13. Chalkiadaki, A.; Guarente, L. High-fat diet triggers inflammationinduced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction. Cell. Metab. 2012, 16, 180–188.
• 14. Chang YC, Hee SW, Hsieh ML, Jeng YM, Chuang LM (2015). The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment. Anal Cell Pathol (Amst) 2015: 972891. http://dx.doi.org/10.1155/2015/972891.
• 15. Chang E, Kim Y (2017). Vitamin D Insufficiency Exacerbates Adipose Tissue Macrophage Infiltration and Decreases AMPK/ SIRT1 Activity in Obese Rats. Nutrients 2017, 9, 338; doi:10.3390/ nu9040338. www.mdpi.com/journal/nutrients.
• 16. de Souza WN, Martini LA (2015). The role of Vitamin D in obesity and inflammation at adipose tissue. J Obes Metab Res. 2: 161-166.
• 17. Dinca M, Serban M, Sahebkar A, Mikhailidis D, Toth P, Martin S, et al (2016). Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and metaanalysis of randomized controlled trials. Pharmacol Res.107:360-71
• 18. Ding C, Gao D, Wilding J, Trayhurn P and Bing C (2012). Horizons in Nutritional Science. Vitamin D signalling in adipose tissue. Br J Nutr. 108 (11):1915-1923.
• 19. Fontana, L.; Eagon, J.C.; Trujillo, M.E.; Scherer, P.E.; Klein, S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007, 56, 1010–1013.
• 20. Gaidhu, M.P.; Anthony, N.M.; Patel, P.; Hawke, T.J.; Ceddia, R.B. Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: Role of ATGL, HSL, and AMPK. Am J Physiol. Cell. Physiol. 2010, 298, C961–C971.
• 21. Galic, S.; Fullerton, M.D.; Schertzer, J.D.; Sikkema, S.; Marcinko, K.;Walkley, C.R.; Izon, D.; Honeyman, J.; Chen, Z.P.; van Denderen, B.J.; et al. Hematopoieti-educes mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Investig 2011, 121, 4903-4915.
• 22. Gallagher JC, Sai A, Templin I, Thomas Smith L (2012). Dose Response to Vitamin D Supple- mentation in Postmenopausal Women. A Randomized Trial. Ann Intern Med.156 (6):425-437
• 23. Gao D, Trayhurn P, Bing C (2013). 1,25-dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int J Obes, 37, 357- 365.
• 24. Gauthier MS, O’Brien EL, Bigornia S, Mott M, Cacicedo JM, Xu XJ, Gokce N, Apovian C, Ruderman N (2011). Decreased AMPactivated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans. Biochem. Biophys. Res. Commun., 404, 382–387.
• 25. Gesta S, Tseng YH and Kahn CR (2007). Developmental origin of fat: tracking obesity to its source. Cell, 131 (2): 242–256.
• 26. Ghavamzadeh S, Mobasseri M, Mahdavi R (2014). The Effect of Vitamin D Supplementation on Adiposity, Blood Glycated Hemoglobin, Serum Leptin and Tumor Necrosis Factor-α in Type 2 Diabetic Patients. Int J Prev Med,.5 (9): 1091–1098.
• 27. Gillum MP, Kotas ME, Erion DM, Kursawe R, Chatterjee P, Nead KT, Muise ES, Hsiao JJ, Frederick DW, Yonemitsu S et al.. (2011). Sirt1 regulates adipose tissue inflammation. Diabetes 60, 3235– 3245.
• 28. Goldner WS, Stoner JA, Thompson J, Taylor K, Larson L, Erickson J, McBride C (2008). Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: A comparison with nonobese controls. Obes. Surg. 18,145-150.
• 29. Gonzalez-Molero I, Rojo-Martinez G, Morcillo S, Gutierrez C, Rubio E, Perez-Valero V, Esteva I, Ruiz de Adana MS, Almaraz MC, Colomo N et al.. (2013). Hypovitaminosis D and incidence of obesity: A prospective study. Eur J Clin Nutr 67, 680–682.
• 30. Holick MF (2004). Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. The American Journal of Clinical Nutrition. 80 (6 Suppl): 1678S–1688S.
• 31. Jonas MI, Kurylowicz A, Bartoszewicz Z,Lisik W,Jonas M,Wierzbicki Z et al (2015). Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue, but Obesity Is Associated with Their Increased Content in Visceral Fat Depots. Int J Mol Sci. 16(10): 25817–25830.
• 32. Kershaw EE, Flier JS (2004). Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 89 (6): 2548-2556.
• 33. Kong J., Li YC (2006). Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3t3-l1 cells. Amer. J. Physiol. Endocrinol. Metab. 290: E916 – E924.
• 34. Koszowska A, Nowak J, Dittfeld A, Brończyk-Puzoń A, Kulpok A, Zubelewicz-Szkodzińska B (2014). Obesity, adipose tissue function and the role of vitamin D. Cent Eur J Immunol. 2:260-264
• 35. Laflamme DP (2012). Companion Animals Symposium: Obesity in dogs and cats: What is wrong with being fat? J. Anim. Sci. 2012.90:1653–1662.
• 36. Lago F, Dieguez C, Gómez-Reino J and Gualillo O (2007). Adipokines as emerging mediators of immune response and inflammation. Nature Clinical Practice Rheumatology, 3 (12): 716–724.
• 37. Lorente-Cebrian S, Eriksson A, Dunlop T, Mejhert N, Dahlman I, Astrom G, Sjolin E, Wahlen K, Carlberg C, Laurencikiene J et al.. (2012). Differential effects of 1 alpha, 25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes. Eur. J. Nutr. 2012, 51, 335–342.
• 38. Maggi S, Siviero P, Brocco E, Albertin M, Romanato G, Crepaldi G (2013). Vitamin D deficiency, serum leptin and osteoprotegerin levels in older diabetic patients: an input to new research avenues. Acta Diabetol. 51 (3): 461–469.
• 39. Mutt SJ, Karhu T, Lehtonen S, Lehenkari P, Carlberg C, Saarnio J, Sebert S, Hypponen E, Jarvelin MR, Herzig KH (2012). Inhibition of cytokine secretion from adipocytes by 1,25-dihydroxyvitamin D (3) via the NF-κB pathway. FASEB J. 26, 4400-4407.
• 40. Pappas S (2010). Obesity On the Rise in Animals. Live Science Contributor | November 23. http://www.livescience.com/10277obesity-rise-animals.html. Erişim tarihi: 27.04.2017.
• 41. Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB (2015). Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 16 (4): 341-349.
• 42. Rodriguez-Rodriguez E, Aparicio A, Andres P, Ortega RM (2014). Moderate Vit D deficiency and inflammation related markers in overweight/obese schoolchildren.Int.J.Vitam.Nutr.Res.,84, 98107.
• 43. Rossmeisl M, Flachs P, Brauner P, Sponarova J, Matejkova O, Prazak T, Ruzickova J, Bardova K, Kuda O, Kopecky J (2004). Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores. Int. J. Obes. Relat. Metab. Disord 28 (Suppl4), S38-S44.
• 44. Selting KA, Sharp CR, Ringold R, Thamm DH, Backus R (2014). Serum 25-hydroxyvitamin D concen- trations in dogs-correlation with health and cancer risk. Vet Comp Oncol./vco.12101.
• 45. Seppa N. Link between obesity and vitamin D clarified. People carrying gene variants tied to weight also prone to deficiency. Science News. February 5, 2013. https://www.sciencenews.org/article/ link-between-obesity-and-vitamin-d-clarified.
• 46. Sergeev I. (2009). 1,25-dihydroxyvitamin D3 induces Ca2+mediated apoptosis in adipocytes via activation of calpain and caspase-12. Biochem. Biophys. Res. Commun. 384:18–21.
• 47. Silver R J (2015). Vitamin D In Dogs & Cats. Intrgrative Veteriner Care. http://ivcjournal.com/vitamin-d-in-dogs-cats/
• 48. Skurk, T.; Alberti-Huber, C.; Herder, C.; Hauner, H. Relationship between adipocyte size and adipokine expression and secretion. J. Clin. Endocrinol. Metab. 2007, 92, 1023–1033.
• 49. Soskić S, Stokić E, Isenović ER. The relationship between vitamin D and obesity. Obes Rev. 2012 Jul;13 (7): 592 - 605.
• 50. Spalding, K.L.; Arner, E.; Westermark, P.O.; Bernard, S.; Buchholz, B.A.; Bergmann, O.; Blomqvist, L.; Hoffstedt, J.; Naslund, E.; Britton, T.; et al. Dynamics of fat cell turnover in humans. Nature 2008, 453, 783–787.
• 51. Spoto B, Di Betta E, Mattace-Raso F, Sijbrands E, Vilardi A, Parlongo RM, et al. Pro- and anti-inflammatory cytokine gene expression in subcutaneous and visceral fat in severe obesity. Nutr Metab Cardiovasc Dis. 2014;24 (10): 1137–1143.
• 52. Sun X, Zemel MB (2007). Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity 15, 340-348.
• 53. Sun X, Zemel MB (2008). Calcitriol and calcium regulate cytokine production and adipocyte-macrophage cross-talk. J. Nutr. Biochem. 19, 392–399.
• 54. Trayhurn P, Beattie JH (2001). Physiological role of adipose tissue: White adipose tissue as an endocrine and secretory organ. Proc. Nutr. Soc. 60, 329–339.
• 55. Tremblay S, 2015. Vitamin D and Hormonal Imbalances.
• 56. Tripathi YB, Pandey V (2012). Obesity and endoplasmic reticulum stresses. Front Immunol. 3240.
• 57. Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, et al. (2013). Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 10 (2): e1001383. http://dx.doi.org/10.1371/ journal.pmed.1001383.
• 58. Wakshlag JJ, Strube AM, Levine CB et al., (2011). The effects of weight loss on adipokines and markers of inflammation in dogs. Br J Nutr. 106: S11- S14.
• 59. Watkins RR, Lemonovich TL, Salata RA (May 2015). “An update on the association of vitamin D deficiency with common infectious diseases”. Canadian Journal of Physiology and Pharmacology. 93 (5): 363–368.
• 60. Weisberg SP; McCann D; Desai M; Rosenbaum M; Leibel RL; Ferrante AW Jr (2003). Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Investig., 112, 1796-1808.
• 61. WHO 2014. World health statistics. http://apps.who.int/iris/bitstre am/10665/112738/1/9789240692671_eng.pdf.
• 62. WHO, 2016. Obesity and overweight. http://www.who.int/mediacentre/factsheets/fs311/en
• 63. Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, Sun XJ, Li YC (2009). Involvement of the vitamin D receptor in energy metabolism: Regulation of uncoupling proteins. Am. J. Physiol. Endocrinol. Metab. 296, E820–E828.
• 64. Wong KE, Kong J, Zhang W, Szeto FL, Ye H, Deb DK, Brady MJ, Li YC (2011). Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J Biol Chem., 286, 33804–33810
• 65. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000). Decreased bioavailability of vitamin D in obesity. American Journal of Clinical Nutrition. Volume 72 (3): 690-693.
• 66. Wozniak SE, Gee L L, Wachtel MS and Frezza EE (2009). Adipose tissue: the new endocrine organ? a review article. Digestive Diseases and Sciences, 54 (9): 1847–1856.
• 67. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA et al.. (2003). Chronic inflam mation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Investig 112, 1821-1830.
• 68. Yang Z, Kahn BB, Shi H, Xue BZ (2010). Macrophage alpha1 AMP-activated protein kinase (alpha1AMPK) antagonizes fatty acid-induced inflammation through SIRT1. J. Biol. Chem, 285, 19051–19059.
• 69. Yılmaz, M (2015). Hayvanlarda Obezite. http://thekedi.com/hayvanlarda-obezite/.
• 70. Zujaja-Tul-Noor Hamid Mehmood and Dimitrios Papandreou (2014). An Updated Mini Review of Vitamin D and Obesity: Adipogenesis and Inflammation State. Front Physiol. 24; 5, 228.
• 71. Zemel MB. (2002). Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications. J Am Coll Nutr. 21: 146S–151S.
• 72. http://www.haberturk.com/saglik/haber/1044090. Erişim tarihi: 22.04.2017 73. https://en.wikipedia.org/wiki/Vitamin_D. Erişim tarihi: 30.03 2017. 74. https://en.wikipedia.org/wiki/Vitamin_D_deficiency. Erişim tarihi: 30.03.2017