"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). "
The combination effects index (CI) analysis confirmed the synergy of clioquinol and clofibrate on inhibiting cancer cell viability. Using inhibitors to block PPARalpha signaling diminished the synergistic cytotoxicity of clioquinol and DHA. These results provide pharmacological evidence that the synergistic anticancer action of clioquinol and DHA is mediated by PPARalpha signaling in human cancer cells.
PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells.
Tuller ER, Brock AL, Yu H, Lou JR, Benbrook DM, Ding WQ.
Biochem Pharmacol. 2009 May 1;77(9):1480-6. Epub 2009 Feb 13.
PMID: 19426685
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
Vitamin D signaling, infectious diseases, and regulation of innate immunity.
White JH.
Infect Immun. 2008 Sep;76(9):3837-43. Epub 2008 May 27. Review.
PMID: 18505808
doi:10.1128/IAI.00353-08
Scientists have known that cruciferous vegetables contain a host of chemopreventive agents that act in many different ways to block cancer development.2 Key among these products are indole-3-carbinol (I3C) and sulforaphane.1,3
Cancer cells need a brisk blood supply to support their rampant growth and reproduction. Preliminary studies in vitro and in vivo have found that apigenin inhibits blood vessel growth (angiogenesis) in human ovarian cancer cells, blocking production of two main signaling molecules required to stimulate vessel growth.20,21 Scientists confirmed this effect in ovarian cancer cells, also finding that apigenin strongly inhibits cell proliferation.22
Apigenin and BITC: Complementary Cancer Protection
Cancer cells also need energy to support their frenetic reproductive activity. Researchers applied apigenin to human pancreatic cancer cells in culture and studied the cells' uptake of glucose.14 Astonishingly, they found that apigenin deprived energy-hungry cancer cells of glucose to support their voracious appetites and aggressive growth. It did this by down-regulating vital glucose-transporting proteins in cancer cells. This approach could effectively starve deadly cancer cells and stop them in their tracks.
Another cruciferous vegetable component receiving rave reviews is the sulfur-containing molecule benzyl isothiocyanate, or BITC (pronounced "bitsy"). As with apigenin, population studies have shown that higher intakes of BITC correlate with reduced risk of cancers of the lung, breast, and colon30 while blocking cancer development in a host of different ways.
BITC induces breast cancer cell death by apoptosis (programmed cell death), interfering with cancer cells' energy utilization and causing them to die off before they can contribute to tumor growth.31,32 In human ovarian cancer cells, BITC induces apoptosis by a different mechanism. It stimulates "signaling" molecules that tell cancer cells it's time to close up shop.
Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production.
Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK.
J Biol Chem. 2005 Nov 18;280(46):38445-56. Epub 2005 Sep 9.
PMID: 16155293
doi: 10.1074/jbc.M508159200
Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA promotes NFkappaB activation and subsequent induction of IL-6, which are at least in part responsible for trans-10, cis-12 CLA-mediated suppression of peroxisome proliferator-activated receptor gamma target gene expression and insulin sensitivity in mature human adipocytes.
In summary, our in vitro data demonstrate that a physiological level of trans-10, cis-12 CLA activates NFκB- and ERK1/2-dependent cytokine production, which together suppress PPARγ and Glut4 levels and lead to impaired glucose uptake. Studies are currently under way examining 1) how CLA regulates PPARγ and the expression of its target genes, 2) the specific signaling role of SV cells and adipocytes in mediating the TG-lowering actions of CLA, and 3) the CLA-induced, upstream signal that activates NFκB and ERK1/2.
As we noted in this article back in July, there are several hormones and neurotransmitters that have noteworthy effects on appetite and eating behavior, and as a result are of much interest with respect to weight gain (or loss) and obesity. The two mentioned in that article were NPY and PYY. The protein leptin is another hormone of this sort. It is often discussed in connection with obesity, because it is believed to increase metabolism and decrease appetite (as a signal of satiety). Another hormone, ghrelin, is produced in the stomach as a signal of hunger, and so it increases appetite.
Natural Sphingadienes Inhibit Akt-Dependent Signaling and Prevent Intestinal Tumorigenesis.
Fyrst H, Oskouian B, Bandhuvula P, Gong Y, Byun HS, Bittman R, Lee AR, Saba JD.
Cancer Res. 2009 Nov 24. [Epub ahead of print]
PMID: 19934323
DOI: 10.1158/0008-5472.CAN-09-2341
What is C-reactive protein (CRP)?
It is a blood-borne protein that originates in the liver and serves as an index of the body's inflammatory state. It is triggered by yet another inflammatory signal molecule, interleukin-6.
What triggers this cascade of inflammatory markers? Any inflammatory stimulus, such as being overweight, lack of exercise, vitamin D deficiency, viral illness no matter how trivial, any inflammatory disease like arthritis, small LDL, high triglycerides, poor diet rich in processed foods, resistance to insulin, any injury, incipient diabetes, hidden cancer, lack of education (no kidding), etc.
A signalling pathway that influences how sensitive cancer cells are to the beneficial effects of dietary restriction is described in this week's Nature.
Dietary restriction - eating less calories while maintaining essential vitamins and minerals - can extend lifespan, and reduce cancer incidence and growth. But some types of cancer cell are more sensitive to the anti-growth effects of dietary restriction than others, Nada Kalaany and David Sabatini report. The effect hinges on the activity of the phosphatidylinositol-3-kinase (PI3K) pathway. If the pathway is active, dietary restriction has no effect on cancer cells. However, if the pathway is inactive, tumours are sensitive to dietary restriction.
1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus.
Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C.
Circulation. 2009 Aug 25;120(8):687-98. Epub 2009 Aug 10.
PMID: 19667238
doi: 10.1161/CIRCULATIONAHA.109.856070
Conclusion- These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.
Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation. They are abbreviated as LX, an acronym for lipoxygenase (LO) interaction products. At present two lipoxins have been identified; lipoxin A4 (LXA4) and lipoxin B4 (LXB4)
In biochemistry, eicosanoids are signaling molecules derived from omega-3 (ω-3) or omega-6 (ω-6) fats. They exert complex control over many bodily systems, especially in inflammation, immunity and as messengers in the central nervous system. The network
Vitamin K2 is produced by animal tissues, including the mammary glands, from vitamin K1, which occurs in rapidly growing green plants.
A growing body of published research confirms Dr. Price's discoveries, namely that vitamin K2 is important for the utilization of minerals, protects against tooth decay, supports growth and development, is involved in normal reproduction, protects against calcification of the arteries leading to heart disease, and is a major component of the brain.
Vitamin K2 works synergistically with the two other "fat-soluble activators" that Price studied, vitamins A and D. Vitamins A and D signal to the cells to produce certain proteins and vitamin K then activates these proteins.
Vitamin K2 plays a crucial role in the development of the facial bones, and its presence in the diets of nonindustrialized peoples explains the wide facial structure and freedom from dental deformities that Weston Price observe