Modern views on the metabolism and biological effects of vitamin D
Keywords:vitamin D metabolism, pleiotropic extraskeletal effects, review
Vitamin D is a steroid hormone that plays a crucial role in maintaining normal bone condition and calcium homeostasis. In recent years, vitamin D has become a hot topic of endocrinological research, largely Due to the COVID-19 pandemic and the likely correlation between hypovitaminosis D and a high risk of chronic lung disease and associated mortality. Recent studies have shown that vitamin D exhibits a complex multistage metabolism and acts as a hormone on many extracellular targets. This review examines some new intriguing and as yet unclear aspects of vitamin D metabolism, such as new concepts of enzyme regulation, new pleiotropic effects of vitamin D receptor activation (VDR), and epigenetic effects. The mechanisms of vitamin D synthesis in the skin, its metabolism in the hepatic cytochrome P450 system, catabolism, metabolites and transport, gene control and epigenetic modulation are considered in Detail. In addition to the well-known role of vitamin D in calcium and bone metabolism, it has many pleiotropic extraskeletal effects, including potent effects on the immune system, cardiovascular system, adipose tissue and glucose/lipid metabolism, muscle and more. Experimental studies have shown that VDRs are expressed by cancer cell lines. Recent studies have shown a link between low levels of vitamin D and almost all aspects of the metabolic syndrome, such as type 2 diabetes, fasting blood glucose, hypertension, dyslipidemia, obesity and insulin resistance. Several studies have focused on the role of vitamin D in adipose tissue biology. In particular, a negative correlation between vitamin D and leptin or resistin is shown, as well as an inverse correlation with adiponectin. Recent studies in vitamin D-deficient mice have shown impaired secretion of glucose-stimulated insulin by pancreatic islets. Vitamin D is thought to play a role in the pathogenesis and progression of cancer, and vitamin D analogues can slow cancer progression and metastasis. It is concluded that vitamin D is a molecule with several endocrine, paracrine and autocrine effects on many tissues and organs, in addition to maintaining skeletal homeostasis. Research in this area, which aims to clarify the pleiotropy of many effects of vitamin D and its metabolites, continues.
Giustina A, Adler RA, Binkley N, et al. Consensus statement from 2nd International Conference on Controversies in Vitamin D. Rev Endocr Metab Disord. 2020;21(1):89-116. doi: 10.1007/s11154-019-09532-w.
Mitsche MA, McDonald JG, Hobbs HH, Cohen JC. Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways. Elife. 2015 Jun 26;4:e07999. doi: 10.7554/eLife.07999.
Prabhu AV, Luu W, Sharpe LJ, Brown AJ. Cholesterol-mediated Degradation of 7-Dehydrocholesterol Reductase Switches the Balance from Cholesterol to Vitamin D Synthesis. J Biol Chem. 2016;291(16):8363-73. doi: 10.1074/jbc.M115.699546.
Khammissa RAG, Fourie J, Motswaledi MH, Ballyram R, Lemmer J, Feller L. The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health. Biomed Res Int. 2018;2018:9276380. doi: 10.1155/2018/9276380.
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 May 18;101(20):7711-5. doi: 10.1073/pnas.0402490101.
Aatsinki SM, Elkhwanky MS, Kummu O, et al. Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes. Diabetes. 2019;68(5):918-931. doi: 10.2337/db18-1050.
Makris K, Sempos C, Cavalier E. The measurement of vitamin D metabolites: part I-metabolism of vitamin D and the measurement of 25-hydroxyvitamin D. Hormones (Athens). 2020 Jun;19(2):81-96. doi: 10.1007/s42000-019-00169-7.
Volmer DA, Mendes LR, Stokes CS. Analysis of vitamin D metabolic markers by mass spectrometry: current techniques, limitations of the "gold standard" method, and anticipated future directions. Mass Spectrom Rev. 2015;34(1):2-23. doi: 10.1002/mas.21408.
Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M. Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol. 2014;144 Pt A:132-7. doi: 10.1016/j.jsbmb.2013.09.012.
Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A. Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord. 2017;22(1):27-41. doi: 10.1007/s40519-016-0312-6.
Pereira F, Barbáchano A, Silva J, et al. KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells. Hum Mol Genet. 2011;20(23):4655-65. doi: 10.1093/hmg/ddr399.
Zhou YF, Luo BA, Qin LL. The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies. Medicine (Baltimore). 2019;98(38):e17252. doi: 10.1097/MD.0000000000017252.
Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi: 10.1136/bmj.i6583.
Soilu-Hänninen M, Aivo J, Lindström BM, et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(5):565-71. doi: 10.1136/jnnp-2011-301876.
Pankiv VI, Yuzvenko TYu, Pankiv I. Type 2 diabetes mellitus and subclinical hypothyroidism: focusing on the role of cholecalciferol. Problems of Endocrine Pathology. 2019;68(2):46-51. doi: 10.21856/j-PEP.2019.2.07.
Stokić E, Kupusinac A, Tomic-Naglic D, Smiljenic D, Kovacev-Zavisic B, Srdic-Galic B, Soskic S, Isenovic ER. Vitamin D and Dysfunctional Adipose Tissue in Obesity. Angiology. 2015;66(7):613-8. doi: 10.1177/0003319714543512.
Colston K, Colston MJ, Feldman D. 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology. 1981 Mar;108(3):1083-6. doi: 10.1210/endo-108-3-1083.
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