Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism—Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer
Abstract
:1. Introduction
2. The Role of Vitamin D and SIRT1 in Healthy Metabolic Regulation of Different Tissues
2.1. Modes of Action of Vitamin D
2.2. Role of Vitamin D in Lipid Metabolism
2.3. Role of Vitamin D in Cardiovascular System
2.4. Role of Vitamin D in the Immune System
2.5. Role of Vitamin D in Redox Homeostasis
2.6. Role of SIRT1 in Healthy Metabolic Regulation
2.7. Connection and Importance of Circadian Rhythm in SIRT1-Regulated Metabolism
3. Vitamin D and SIRT1 in Relation to Non-Communicable Diseases Including Cancer
3.1. Effect of Vitamin D and SIRT1 on Metabolic Syndrome
3.2. Effect of Vitamin D and SIRT1 on CVD
3.3. Effect of Vitamin D and SIRT1 on CKD
3.4. Effect of Vitamin D and SIRT1 on Immune System-Related Diseases
3.5. Effect of Vitamin D and SIRT1 on Cancer Cells
4. Cooperation of Vitamin D and SIRT1 Pathways
4.1. Direct Interaction of Vitamin D and SIRT1
4.1.1. Interaction through Binding of VDR to SIRT1 Promoter Region
4.1.2. Interaction through Binding of VDR to SIRT1 Protein or via Epigenetic Modifications of Each Other
4.2. Indirect Interaction of Vitamin D and SIRT1
5. Potential Applications of Vitamin D and Induction of SIRT1 in the Prevention, Treatment, and Reduction of Mortality Risk of Non-Communicable Diseases
5.1. Guidelines for Vitamin D Status and Its Daily Intake
5.2. Recommendation for Healthy Individuals to Achieve the 30–50 ng/mL of Serum 25(OH)D3 Level
5.3. Recommendation for Patients with Diseases to Achieve the 30–50 ng/mL of Serum 25(OH)D3 Level
5.4. Recommendation to Maintain an Optimal SIRT1 Level in the Body
5.5. Recommendation to Preventive and Complementary Treatments
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Number | Key Vitamin D Target Genes | Location | Function | Processes | Ref |
---|---|---|---|---|---|
1 | ACVRL1 | plasma membrane | TGF-β receptor//serine/threonine kinases | signaling | [77] |
2 | CD14 | plasma membrane | TLR coreceptor | innate immunity | |
3 | CD93 | plasma membrane | intercellular adhesion, clearance of apoptotic cells | innate immunity | |
4 | LILRB4 | plasma membrane | leukocyte immunglobulin-like receptor (LIR) | inhibiting immune response | |
5 | LRRC25 | membrane bound in the cytoplasm | inhibition of IFN and NFκB signaling pathways | inhibiting immune response | |
6 | NINJ1 | plasma membrane | adhesion molecule | inflammation, cell death, axonal growth, cell chemotaxis, and angiogenesis | |
7 | SEMA6B | plasma membrane | axon guidance | NS development | |
8 | THBD | plasma membrane | thrombin receptor | coagulation | |
9 | TREM1 | plasma membrane | receptor (Ig superfamily member) | amplifies neutrophil and monocyte-mediated inflammatory responses | |
10 | CAMP | secreted | antimicrobial peptid | innate immunity | |
11 | FN1 | plasma membrane, extracellular matrix, secreted into the plasma (blood) | glycoprotein | cell adhesion and migration processes (embryogenesis, wound healing, blood coagulation, host defense, and metastasis) | |
12 | SRGN | secretory granules in hemapoetic cells | secretory granule formation, mediator of cytotoxic cell granule-mediated apoptosis, regulates MMP2 and TNF-α secretion, inhibits bone mineralization | innate and adaptive immunity, Ca2+ homesotasis | |
13 | CEBPB | nucleus | transcription factor, regulation of immune and inflammatory response, adipogenesis, gluconeogenesis, liver regeneration, hematopoesis, osteoblast differentiation, osteoclastogenesis | innate and adaptive immunity, metabolism, bone hoeostasis | |
14 | THEMIS2 | cytoplasm and nucleus | T cell receptor signaling, regulation of B cell activation, macrophage inflammatory response, promotes LPS-induced TLR4-mediated TNF production | innate and adaptive immunity | |
15 | MAPK13 | cytoplasm (member of MAP kinase family, a p38 MAP kinase) | mediates extracellular stimuli; activating ELK1, ATF2 trascription factors, prolactin signaling, | innate and adaptive immunity, proliferation, differentiation, transcription regulation, development | |
1 | CYP24A1 | mitochondria | degradation of 1,25-dihydroxyvitamin D3, calcium homeostasis, | vitamin D endocrine system | [83] |
2 | G0S2 | mitochondria | positive regulation of extrinsic apoptotic pathway, binding to BCL2 | regulation of apoptosis | |
3 | HBEGF | secreted, extracellular space | growth factor | SMC proliferation, cardiac valve formation, normal heart function | |
4 | SEMA6B | type I membrane protein | cell surface repellent | axon guidance | |
5 | THBD | endothelial specific type I membrane receptor | receptor of thrombin | bind thrombin, conversion of protein C to activated protein C | |
6 | AQP9 | plasma membrane, multi pass membrane protein | water channel | permeable for glyerol and urea, mediate passage of small, non-charged solutes (carbamides, polyols, purines, pyrimidines) | |
7 | CCL7 | secreted | chemotactic factor, attracts moncytes and eosinophils but not neutrophils, binds heparin, CCR1/2/3 | attracts macrophages during inflammation and metastasis, augments monocytes antitumor activity, induces release of gelatinase B | |
8 | PVALB | cytoplasm, nucleoplasm | high-affinity calcium binding | muscle relaxation in muscle cells, calcium binding in GABAergic cells | |
9 | CD1E | plasma membrane, MHC-type protein | form heterodimers with beta-2-microglobulin | presentation of lipid and glycolipid antigens to T cells | |
10 | NRG1 | plasma membrane, single-pass type I membrane protein | ligand of ERBB3/4 tyrosine kinase receptors | growth, differentiation of epithelial, glial, neuronal and skeletal muscle cells, stimulating milk production, mammary tumor cell differentiation | |
1 | CD14 | plasma membrane | TLR co-receptor | innate immunity (independent of the size of the tested target gene set, gene ontology analysis indicates that the modulation of innate immunity is the main physiological outcome of a vitamin D stimulation of human monocytes) | [84] |
2 | ORM1 | vesicles in the cytoplasm | acute phase plasma protein | ||
3 | CAMP | secreted | antimicrobial peptid | ||
4 | FBP1 | mitochondria | glucose metabolizing enzyme | ||
5 | CYP26B1 | endoplasmatic reticulum | Drug- and retinoid metabolism, and synthesis of cholesterol, steroids and other lipids | ||
6 | TSPAN18 | plasma membrane | unknown | ||
7–19 | +13 other genes | top five biological pathways: neutrophil activation, positive regulation of TNF production, inflammatory response, neutrophil degranulation, negative regulation of T cell proliferation, positive regulation of cytokine secretion |
25(OH)D3 Level (ng/mL) | Recommendation of IOM | Recommendation of ES |
---|---|---|
lower than 12 | deficiency | deficiency |
12–19 | inadequacy | deficiency |
20–29 | sufficiency | insufficiency |
30–49 | sufficiency | sufficiency |
higher than 50 | reason for concern | sufficiency |
Vitamin D | SIRT1 | Tissue/Organ Type | Diseases | Signal Pathway/Targeted Molecules | Prevention/Complementary Treatment Options |
---|---|---|---|---|---|
decrease: BMI, body fat, TGs, CRP, TNFα. increase: SIRT1/6, HDL-C, apo-AI, ABCA1, FFA oxidation | decrease: adipocyte differentiation-PPARγ, inflammation, leptin increase: activates PPAR-α, lipolysis, FFA oxidation, PGC-1α, insulin/mTOR/cell growth, leptin/PI3K-Akt-mTORC1 | adipose (white/brown) | T2DM, obesity, insulin resistance | adiponectin/NFĸB, AMPK, PPAR-α | • weight loss • exercise/physical activity • emotional/mental support • nutrition factors (vitamin D, polyphenols, carotinoids, omega-3 FA) |
increase: glucose uptake and utilization | increase: FFA oxidation, PGC-1α | skeltal muscle | insulin resistance | adiponectin/NFĸB, AMPK, PPAR-α | |
increase: NO production, fat oxidation decrease: blood pressure, cardiac hypertophy, foam cell formation, macrophage activation, vascular inflammation, oxidative stress | decrease: cardiac hypertophy, proinflammatory macrophage activity increase: PPAR-α, eNOS/NO, FOXOs | endothel | cardiovascular abnormalities | adiponectin/NFĸB, AMPK, PPAR-α | |
decrease: renin-angiotensin-aldosterone axis | kidney | CKD, hypertension | |||
decrease: inflammation, proinflammatory cytokines, TNFα and CRP, mTOR, ROS/RNS increase: IL-10, IL-1RA, BCAA catabolism, antioxidant enzymes | decrease: TLR4, IFNγ, IL-1β, IL-6, IL-8 and TNFα levels, oxidative stress, ROS, iNOS, COX-2 | immune system | TLR4 Akt/NFĸB/COX-2, Nrf2 | ||
decrease: β-catenin, WNT/β-catenin pathway, c-Myc, TCF1, LEF1, antiapoptotic proteins, HIF-1, VEGF, IL-8 increase: p21WAF/CIP and p27KIP, E-cadherin, DKK-1, proapoptotic proteins, Nrf2 | decrease: NFκB, MMP-9, insulin/mTOR/cell growth, leptin/PI3K-Akt-mTORC1, TNF-α, IL-1β, iNOS, COX-2; initiation, promotion, and progression of cancer development increase: ROS, apoptosis, cell cycle arrest | PC, BC, CRC, SkinC | cancer | insulin/mTOR/cell growth, proliferation of leptin/PI3K-Akt-mTORC1 |
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Nemeth, Z.; Patonai, A.; Simon-Szabó, L.; Takács, I. Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism—Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer. Int. J. Mol. Sci. 2023, 24, 6154. https://doi.org/10.3390/ijms24076154
Nemeth Z, Patonai A, Simon-Szabó L, Takács I. Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism—Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer. International Journal of Molecular Sciences. 2023; 24(7):6154. https://doi.org/10.3390/ijms24076154
Chicago/Turabian StyleNemeth, Zsuzsanna, Attila Patonai, Laura Simon-Szabó, and István Takács. 2023. "Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism—Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer" International Journal of Molecular Sciences 24, no. 7: 6154. https://doi.org/10.3390/ijms24076154