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n-3 fatty acids and gene expression. Deckelbaum RJ, Worgall TS, Seo T. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1520S-1525S. Review. Erratum in: Am J Clin Nutr. 2006 Oct;84(4):949. PMID: 16841862 Accumulating evidence in both humans and animal models clearly indicates that a group of very-long-chain polyunsaturated fatty acids, the n-3 fatty acids (or omega-3), have distinct and important bioactive properties compared with other groups of fatty acids. n-3 Fatty acids are known to reduce many risk factors associated with several diseases, such as cardiovascular diseases, diabetes, and cancer. The mechanisms whereby n-3 fatty acids affect gene expression are complex and involve multiple processes. As examples, n-3 fatty acids regulate 2 groups of transcription factors, such as sterol-regulatory-element binding proteins and peroxisome proliferator-activated receptors, that are critical for modulating the expression of genes controlling both systemic and tissue-specific lipid homeostasis. Modulation of specific genes by n-3 fatty acids and cross-talk between these genes are responsible for many effects of n-3 fatty acids.

Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses. This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects

DHA and EPA generally modulated different sets of genes, although a few common effects were noted. In our approach, we used preneoplastic adenoma cells which are a relevant model for target cells of chemoprevention. If verified with real time PCR, these results identify genes and targets for chemoprevention of colon cancer. Modulation of gene expression in eicosapentaenoic acid and docosahexaenoic acid treated human colon adenoma cells. Habermann N, Lund EK, Pool-Zobel BL, Glei M. Genes Nutr. 2009 Mar;4(1):73-6. Epub 2009 Feb 21. PMID: 19234733 doi: 10.1007/s12263-009-0112-y.

"As far as I can tell, MK-4 is capable of performing all the functions of vitamin K. MK-4 can even activate blood clotting factors, which is a role traditionally ascribed to vitamin K1. Babies are often born clotting deficient, which is why we give newborns vitamin K1 injections in the U.S. to prevent hemorrhaging. In Japan, they give children MK-4 to prevent hemorrhage, an intervention that is very effective. Could that have to do with the fact that Japan has half the infant mortality rate of the U.S.? Today, I found another difference between MK-4 and MK-7. I was reading a paper about SXR-independent effects of vitamin K2 on gene expression. The investigators found that MK-4 strongly activates transcription of two specific genes in osteoblast cells. Osteoblasts are cells that create bone tissue. The genes are GDF15 and STC2 and they're involved in bone and cartilage formation. They tested K1 and MK-7, and in contrast to MK-4, they did not activate transcription of the genes in the slightest. This shows that MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have. That being said, MK-7 may still have a place in a healthy diet. Just because it can't do everything MK-4 can, doesn't mean it has no role. It may be able to fill in for MK-4 in some functions, or reduce the dietary need for MK-4. But no one really knows at this point. Hunter-gatherers would have had a source of longer menaquinones, including MK-7, from livers. So it's possible that we're adapted to a modest MK-7 intake on top of MK-4. "

"ScienceDaily (Dec. 26, 2009) - Going back for a second dessert after your holiday meal might not be the best strategy for living a long, cancer-free life say researchers from the University of Alabama at Birmingham. That's because they've shown exactly how restricted calorie diets -- specifically in the form of restricted glucose -- help human cells live longer. They found that the normal cells lived longer, and many of the precancerous cells died, when given less glucose. Gene activity was also measured under these same conditions. The reduced glucose caused normal cells to have a higher activity of the gene that dictates the level of telomerase, an enzyme that extends their lifespan and lower activity of a gene (p16) that slows their growth. Epigenetic effects (effects not due to gene mutations) were found to be a major cause in changing the activity of these genes as they reacted to decreased glucose levels. "Western science is on the cusp of developing a pharmaceutical fountain of youth" said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This study confirms that we are on the path to persuading human cells to let us to live longer, and perhaps cancer-free, lives.""

"November 26, 2008 New evidence may explain why it is that we lose not only our youthful looks, but also our youthful pattern of gene activity with age. A report in the November 26th issue of the journal Cell, a Cell Press publication, reveals that a protein perhaps best known for its role in the life-extending benefits of a low-calorie diet also maintains the stability of the mammalian genome-the complete set of genetic instructions "written" in DNA. The researchers found in studies of mammalian stem cells that the protein SIRT1 controls the packaging of DNA into chromatin, thereby setting the youthful pattern of gene activity by keeping select genes switched off. In response to DNA damage, those SIRT1 proteins leave their posts to go off and assist in the necessary repairs. That change in SIRT1's job description leads to shifts in gene activity that parallel those seen in the aging mouse brain, they show. They suspect similar changes would also be found in other body tissues as well."

"My goal is to gather the basic science and apply it to nutrition - NUTRIGENOMICS. What do I mean? How does what we eat signal our genes in the nucleus. By our food choices, we are sending different signals to our genes. High carbohydrate and high fructose intake signals it is summer time and winter is coming -- grow and store the energy (insulin). High fat, low carbohydrate diet with calorie restriction signals our genes that winter is here -- use the stored energy, repair the genes, and slow down growth (i.e. Sirt1/Foxo pathway). The Sirt1/FoxO1 pathway is important as it aids in repairing DNA. Damaged DNA can lead to uncontrolled cellular replication (i.e. cancers). The immune system (phagocytes) has a mechanism to remove old and unwanted cells called apoptosis (cellular death). "

Your cells use vitamin D to directly regulate your genes, making it one of the most powerful compounds in human health.

Researchers at the University of California, Berkeley, have identified a gene that plays a critical regulatory role in the process of converting dietary carbohydrates to fat. In a new study, they disabled this gene in mice, which consequently had lower levels of body fat than their normal counterparts, despite being fed the equivalent of an all-you-can-eat pasta buffet. The authors of the study, to be published in the March 20 issue of the journal Cell, say the gene, called DNA-PK, could potentially play a role in the prevention of obesity related to the over-consumption of high-carbohydrate foods, such as pasta, rice, soda and sugary snacks..

"THURSDAY, Dec. 3 (HealthDay News) -- New research points to the possibility of a genetic link between vitamin D and heart disease. People with high blood pressure who had a gene variant that reduces vitamin D activation in the body were found to be twice as likely as those without the variant to have congestive heart failure, the study found. The finding may lead to a way to identify people at increased risk for heart disease, according to Robert U. Simpson, an assistant professor of pharmacology at the University of Michigan Medical School and his research colleagues. They analyzed the genetic profiles of 617 people. One-third had hypertension, one-third had hypertension and congestive heart failure, and the remaining third served as healthy controls. The researchers found that a variant in the CYP27B1 gene was associated with congestive heart failure in people with hypertension. The study is in the November issue of Pharmacogenomics."

Use of vitamin D in clinical practice. Cannell JJ, Hollis BW. Altern Med Rev. 2008 Mar;13(1):6-20. PMID: 18377099 The recent discovery--from a meta-analysis of 18 randomized controlled trials--that supplemental cholecalciferol (vitamin D) significantly reduces all-cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Not only are such deficiencies common, and probably the rule, vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone that targets more than 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng per ml, levels obtained by few modern humans. Assessing serum 25-hydroxy-vitamin D (25(OH)D) is the only way to make the diagnosis and to assure treatment is adequate and safe. Three treatment modalities exist for vitamin D deficiency: sunlight, artificial ultraviolet B (UVB) radiation, and vitamin D3 supplementation. Treatment of vitamin D deficiency in otherwise healthy patients with 2,000-7,000 IU vitamin D per day should be sufficient to maintain year-round 25(OH)D levels between 40-70 ng per mL. In those with serious illnesses associated with vitamin D deficiency, such as cancer, heart disease, multiple sclerosis, diabetes, autism, and a host of other illnesses, doses should be sufficient to maintain year-round 25(OH)D levels between 55 -70 ng per mL. Vitamin D-deficient patients with serious illness should not only be supplemented more aggressively than the well, they should have more frequent monitoring of serum 25(OH)D and serum calcium. Vitamin D should always be

Conclusion We demonstrated that the VDRE in the CAMP gene originated from the exaptation of an AluSx SINE in the lineage leading to humans, apes, OWMs and NWMs and remained under purifying selection for the last 55-60 million years. We present convincing evidence of an evolutionarily fixed, Alu-mediated divergence in steroid hormone nuclear receptor gene regulation between humans/primates and other mammals. Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. Gombart AF, Saito T, Koeffler HP. BMC Genomics. 2009 Jul 16;10:321. PMID: 19607716 doi:10.1186/1471-2164-10-321

Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R. Ann N Y Acad Sci. 2009 Sep;1173:515-20. PMID: 19758194 DOI: 10.1111/j.1749-6632.2009.04656.x Discussion: We found no association of the Apal and Taql VDR gene SNPs with MS or with vitamin D metabolism in our population. Further research should assess the complex interaction between vitamin D, the VDR, and susceptibility to MS.

The effect of select nutrients on serum high-density lipoprotein cholesterol and apolipoprotein A-I levels. Mooradian AD, Haas MJ, Wong NC. Endocr Rev. 2006 Feb;27(1):2-16. Epub 2005 Oct 21. Review. PMID: 16243964 One of the factors contributing to the increased risk of developing premature atherosclerosis is low plasma concentrations of high-density lipoprotein (HDL) cholesterol (HDLc). Multiple potential mechanisms account for the cardioprotective effects of HDL and its main protein apolipoprotein A-I (apo A-I). The low plasma concentrations of HDL could be the result of increased fractional clearance and reduced expression of apo A-I. To this end, nutrients play an important role in modulating the fractional clearance rate, as well as the rate of apo A-I gene expression. Because medical nutrition therapy constitutes the cornerstone of management of dyslipidemias, it is essential to understand the mechanisms underlying the changes in HDL level in response to alterations in dietary intake. In this review, we will discuss the effect of select nutrients on serum HDLc and apo A-I levels. Specifically, we will review the literature on the effect of carbohydrates, fatty acids, and ketones, as well as some of the nutrient-related metabolites, such as glucosamine and the prostanoids, on apo A-I gene expression. Because there are multiple mechanisms involved in the regulation of serum HDLc levels, changes in gene transcription do not necessarily correlate with clinical observations on serum levels of HDLc.

The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Gombart AF. Future Microbiol. 2009 Nov;4:1151-65. PMID: 19895218 Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications

These data indicate that fish oil feeding downregulated the endogenous PPAR-activation system and increased antioxidant gene expressions to protect against ROS excess Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production. Takahashi M, Tsuboyama-Kasaoka N, Nakatani T, Ishii M, Tsutsumi S, Aburatani H, Ezaki O. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G338-48. PMID: 11804856

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Chang TJ, Lei HH, Yeh JI, Chiu KC, Lee KC, Chen MC, Tai TY, Chuang LM. Clin Endocrinol (Oxf). 2000 May;52(5):575-80. PMID: 10792336 DOI: 10.1046/j.1365-2265.2000.00985.x CONCLUSIONS Vitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.

NaturalNews) Researchers from Oxford University and the University of British Columbia have discovered that Vitamin D deficiency affects a section of the human genome already linked with multiple sclerosis (MS) risk, adding further weight to theories that this vitamin deficiency might play a role in development of the disease. "Here we show that the main environmental risk candidate -- vitamin D -- and the main gene region are directly linked and interact," said co-author George Ebers.

Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Simmons JD, Mullighan C, Welsh KI, Jewell DP. Gut. 2000 Aug;47(2):211-4. PMID: 10896912 doi:10.1136/gut.47.2.211

A Role of DNA-PK for the Metabolic Gene Regulation in Response to Insulin Roger H.F. Wong, Inhwan Chang, Carolyn S.S. Hudak, Suzanne Hyun, Hiu-Yee Kwan, Hei Sook Sul Cell 20 March, 2009 Volume 136, Issue 6, p1056 doi:10.1016/j.cell.2008.12.040