Reduction of Signalling of GSK-3B May Reduce Some Problems in Non-alcoholic Liver Disease~!

High fat diets may caugment environmental illness by disrupting processes in a variety of pathways such as the Nrf2 and contributes to a variety of patholgies including non-alcoholic liver disease. GSK-3b is a protein that can serve as an "on-off switch" for the antioxidant system. A new study shows that knock-down of this protein may provide cells with more resistance to some of the damaging effects of saturated fats in the diet.

 Ibrahim, S. H. et al. Glycogen synthase kinase-3 (GSK-3) inhibition attenuates hepatocyte lipoapoptosis. Journal of hepatology (2010). URL http://dx.doi.org/10.1016/j.jhep.2010.09.039. http://www.citeulike.org/user/HEIRS/article/8365324

Resistin decreases eNOS and May Play Major Role in Oxidative Stress and Mitochondrial Dysfuntion!

Resistin: Resistin is a protein secreted by immune and epithelial cells in some mammals including primates and dogs and secreted in adipocytes in mice and rats. Recent discoveries of its role include inflammation and energy regulation as well as, observations in playing a part in insulin resistance. (Wipedia)

Three antioxidants, seleno-L-methionine, ginsenoside Rb1, and MnTBAP (superoxide dismutase mimetic), effectively blocked resistin-induced eNOS downregulation....Thus resistin directly induces eNOS downregulation through overproduction of ROS and activation of p38 and JNK in HCAECs. Resistin-induced mitochondrial dysfunction and imbalance in cellular redox enzymes may be the underlying mechanisms of oxidative stress.

HEIRS Library Tags: Resistin

CiteULike: Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells: "Chen, C., Jiang, J., Lu, J.-M., Chai, H., Wang, X., Lin, P. H., and Yao, Q. (2010). Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells. Am J Physiol Heart Circ Physiol, 299(1):H193-201."

Neuroprotection through Stimulation of Mitochondrial Antioxidant Protein Expression.

Nrf2 system and its protection against mitochondrial bioenergetic dysfunction may therefore constitute a powerful mechanism for both pre-conditioning against neurodegeneration and for post-conditioning against neural cell death associated with acute neurologic injury.

CiteULike: Neuroprotection through Stimulation of Mitochondrial Antioxidant Protein Expression.: "Greco, T. and Fiskum, G. (2010). Neuroprotection through stimulation of mitochondrial antioxidant protein expression. Journal of Alzheimer's disease : JAD."

New Culprit In Muscle Defects, Insulin Resistance That Come With Age

Type 2 diabetes is a widespread problem for many people these days, and our risk for insulin resistance and diabetes only grows as we age. Now, a new report in the May issue of Cell Metabolism, a Cell Press publication, reveals a new contributor to the problem: The muscles of elderly people and of people with type 2 diabetes contain lower concentrations of a protein known as PARL (short for "presenilin-associated rhomboid-like").

New Culprit In Muscle Defects, Insulin Resistance That Come With Age

Endocrine disruptor, dioxin (TCDD)-induced mitochondrial dysfunction and apoptosis in human trophoblast-like JAR cells

Endocrine disruptor, dioxin (TCDD)-induced mitochondrial dysfunction and apoptosis in human trophoblast-like JAR cells

The drug MDMA inhibits mitochondrial complex I activity in mice: a possible mechanism underlying neurotoxicity

Inhibition of mitochondrial complex I following MDMA could be the source of free radicals responsible for oxidative stress and the consequent neurotoxicity of this drug in mice.

CiteULike: Methylenedioxymethamphetamine inhibits mitochondrial complex I activity in mice: a possible mechanism underlying neurotoxicity: "Puerta, E., Hervias, I., Goñi-Allo, B., Zhang, S. F., Jordán, J., Starkov, A. A., and Aguirre, N. (2010). Methylenedioxymethamphetamine inhibits mitochondrial complex i activity in mice: a possible mechanism underlying neurotoxicity. British Journal of Pharmacology, 9999(9999)."

Parkinson's and Link To Muscle Protein and Cell Signaling Pathway?

I recently noted that transcription factors such as MEF2, NRF1, NRF2 are co-activated by PGC-1a (important for mitochondrial biogenesis) results in kind of a loop to increase the expression of PGC-1a. PGC-1a regulates a number of transporters that regulate chemicals across membranes and alterations in these proteins may increase or lead to tissue dysfunction.

Recent evidence indicates that chaperone-mediated autophagy plays a role in direct degradation of neuronal transcription factor MEF2D, a protein known to promote neuronal survival. Disruption of this regulatory pathway by α-synuclein leads to neuronal stress, which may underlie neuronal loss in Parkinson’s disease.

For further reading:

• Nrf2's Regulation of NRF1 and Its Influence on NMDA Subunits and Environmental Illness
• Altered Metabolism, Toxicity, Glutamate Dehydrogenase and NRF-1 and Its Activator PGC-1
• Heme Oxygenase-1 Regulates Cardiac Mitochondrial Biogenesis via Nrf2-Mediated Transcriptional Control of Nuclear Respiratory Factor-1 -- Piantadosi et al. 103 (11): 1232 Figure IG7 -- Circulation Research
• Impairments in Muscle Function After Cigarette Exposure and Environmental Illness

Yang, Q. and Mao, Z. (2010). Dysregulation of autophagy and parkinson's disease: the mef2d link. Apoptosis. http://www.citeulike.org/user/HEIRS/article/6715832
Wright, D. C., Han, D.-H. H., Garcia-Roves, P. M., Geiger, P. C., Jones, T. E., and Holloszy, J. O. (2007). Exercise-induced mitochondrial biogenesis begins before the increase in muscle pgc-1alpha expression. The Journal of biological chemistry, 282(1):194-199. http://www.citeulike.org/user/HEIRS/article/6580001
Brockmann, K., Wang, D., Korenke, C. G., Von Moers, A., Ho, Y.-Y., Pascual, J. M., Kuang, K., Yang, H., Ma, L., Kranz-Eble, P., Fischbarg, J., Hanefeld, F., and De Vivo, D. C. (2001). Autosomal dominant glut-1 deficiency syndrome and familial epilepsy. Annals of Neurology, 50(4):476-485. http://www.citeulike.org/user/HEIRS/article/6715941
Hernandez, M. J., Roberts, T. M., and Hardin, C. D. (2007). Caveolin-1 and the organization of glycolysis in astrocytes: Modulation by ammonia. The FASEB Journal, 21. http://www.citeulike.org/user/HEIRS/article/6715979
Klinge, C. M. (2008). Estrogenic control of mitochondrial function and biogenesis. Journal of Cellular Biochemistry, 105(6):1342-1351. http://www.citeulike.org/user/HEIRS/article/3879108

Parkinsons Model Identifies Protein & Mitochondria Metabolic Dysruptions

In Parkinson's disease model, while oxygen consumption is similar to control lines, PD lines demonstrate reduced SIRT1 phosphorylation, lower PGC-1a levels and increased NF-kabbaB activation. Results suggest altered aerobic metabolism and mitochondrial respiration.

Mitochondrial Respiration and Respiration Associated Proteins in Cell Lines Created through Parkinson's Subject Mitochondrial Transfer.: "Raquel Esteves, A., Lu, J., Rodova, M., Onyango, I., Lezi, E., Dubinsky, R., Lyons, K. E., Pahwa, R., Burns, J. M., Cardoso, S. M., and Swerdlow, R. H. (2010). Mitochondrial respiration and respiration associated proteins in cell lines created through parkinson's subject mitochondrial transfer. Journal of neurochemistry."

Elevated Ammonia and Endotoxin: Implications for Synergistic Toxicity in Environmental Illness

Background: I happened on an article this morning that no doubt has important health implications, at least for I and others with impairments of detoxification are concerned. I doubt it evoked much interest by the "Powers That Be" that study this stuff everyday but none-the-less, it seems important for me, not to dismiss it so readily. What I write here are my own thoughts and I by no means am or claim to be, an expert on autism and autistic behavior.

As you may recall, we recently discussed the similiarities of autism and other environmental illnesses including ADHD and multiple chemical sensitivity. Previous studies have shown that certain exposures may inhibit metabolic pathways such the one for production of methionine synthase important for DNA synthesis and repair and may increase concentrations of homocysteine, a potentially toxic byproduct of methionine metabolism. To demonstrate, the inhibition of this pathway by nitrous oxide causes lasting impairment in spatial working memory in aged rats via mitochondrial swelling and subsequent neuronal death.(Culley) In line with this thinking,severa; studies provide evidence that inhibiting or the presense of impairments in pathways such as the one for methionine synthase or others may contribute to a number of mental and physical health conditions including environmental illnesses such as mood disorders, Alzheimer's, autism and MCS.

In the past, I have noted several "remedies" including B12, Q10 and tetrahydrobiopterin recommended for chemical sensitivity which are also commonly used therapies for autism. Curiously, methylhydrofolate is a precursor of BH4 and often prescribed to reduce ammonia levels produced as a side-effect from different supplement treatments and also ammonia produced from gut-derived exogenous bacteria. In addition to hyperammonemia, excess ammonia may lead to elevations in production of nitric oxide synthase and enhanced nitric oxide, free radicals and oxidative stress.

Jalan and Bernuau propose that endotoxin may increase the severity of complications associated with hyperammonemia which of course may have important safety implications for a number of occupational and residential settings including farms and agricultural areas. In this article the authors explain, the "ammonia is detoxified by astrocyctes in the brain". Notably, the deficiency of protective pathways which protect astocytes such as Nrf2 should be an important concern. Jalan further explains that "during hyperammonemia, astrocytes swell from the effect of glutamine. In addition, recent studies show these cells are more swollen in animals exposed to endotoxin and interestingly, the swelling of the atrocytes occur in an environment of an intact blood brain barrier which indicates a functional abnormality. It is assumed that astrocytes are critical managers of blood flow and it may be that during hyperammonemia the astrocytes are sensitized to a "second hit" by LPS endotoxin. The author also proposes other mechanims may be involved in the astrocyte swelling in addition to the ammonia-glutamine hypothesis and one may suggest it includes the activation of P53 and its suppressive effects on Nrf2. (Panickar, Faraonion) The author also mentions pharmacological pre-treatment doses of amiloride, a diuretic used to treat congestive heart failure and hypertension, were required that were 200 fold higher in animals with hyperammonemia in association with exposure to endotoxin." This should demonstrate to anyone whether toxicologically inclined or not, that "something just ain't right",,,,!

He goes on to say, "several substances have been shown to cross the BBB under hepatoxic conditions such as acute liver failure. Incidently, he points out ammonia induces the expression of GLUT1, a transporter across the BBB and this report suggests a non-specific increase in permeability of the BBB and proposes hyperammonia could "unlock" the BBB." It has been shown that ammonia can "alter endothelial cell gene expression and transporter function." (Belanger Of course, this is an important issue to consider whenever a condition of hyperammonemiua occurs. It very well could contribute to the neuroinflammatory consequences in pathological conditions such as autism and conditions that where elevated homocysteine levels impair renal function and as this article suggests, exposures to endotoxin exacerbate related metabolic consequences.

Jalan, R. and Bernuau, J. (2007). Induction of cerebral hyperemia by ammonia plus endotoxin: Does hyperammonemia unlock the blood–brain barrier? Journal of Hepatology, 47(2):168-171. http://www.citeulike.org/user/HEIRS/article/6556614
Essa, M. M. and Subramanian, P. (2006). Hibiscus sabdariffa affects ammonium chloride-induced hyperammonemic rats. eCAM. http://www.citeulike.org/user/HEIRS/article/6556740
Panickar, K. S., Jayakumar, A. R., Rao, K. V. R., and Norenberg, M. D. (2009). Ammonia-induced activation of p53 in cultured astrocytes: Role in cell swelling and glutamate uptake. Neurochemistry International, 55(1-3):98-105. http://www.citeulike.org/user/HEIRS/article/4523207
Faraonio, R., Vergara, P., Di Marzo, D., Pierantoni, M. G. G., Napolitano, M., Russo, T., and Cimino, F. (2006). p53 suppresses the nrf2-dependent transcription of antioxidant response genes. The Journal of biological chemistry, 281(52):39776-39784. http://www.citeulike.org/user/HEIRS/article/4364516?show_msg=already_posted
Culley, D. J., Raghavan, S. V., Waly, M., Baxter, M. G., Yukhananov, R., Deth, R. C., and Crosby, G. (2007). Nitrous oxide decreases cortical methionine synthase transiently but produces lasting memory impairment in aged rats. Anesth Analg, 105(1):83-88. http://www.citeulike.org/user/HEIRS/article/6557028
Bélanger, M., Asashima, T., Ohtsuki, S., Yamaguchi, H., Ito, S., and Terasaki, T. (2007). Hyperammonemia induces transport of taurine and creatine and suppresses claudin-12 gene expression in brain capillary endothelial cells in vitro. Neurochemistry international, 50(1):95-101.
http://www.citeulike.org/group/7833/article/6557716

Recent Links Added to the HEIRS Library!

1. The inhibitory effect of ghrelin on sepsis-induced inflammation is mediated by the MAPK phosphatase-1. http://www.citeulike.org/user/HEIRS/article/6430465#
2.Weight loss, body fat mass, and leptin in Parkinson's disease. http://www.citeulike.org/user/HEIRS/article/6429319
3. High-fat diet induces apoptosis of hypothalamic neurons. http://www.citeulike.org/user/HEIRS/article/4292700
4. Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. http://www.citeulike.org/user/HEIRS/article/6429237
5. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). http://www.citeulike.org/user/HEIRS/article/2997140
6. Sympathetic premotor neurons mediating thermoregulatory functions http://www.citeulike.org/user/HEIRS/article/6429118
7. Up-regulation in expression of vesicular glutamate transporter 3 in substantia nigra but not in striatum of 6-hydroxydopamine-lesioned rats http://www.citeulike.org/user/HEIRS/article/6428977
8. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors http://www.citeulike.org/user/HEIRS/article/6428976
9. Acute and subacute chemical pneumonitis http://www.citeulike.org/user/HEIRS/article/6428868
10. Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase-dependent manner http://www.citeulike.org/user/HEIRS/article/6428693
11. Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and GSK3β) on the risk of Parkinson's disease http://www.citeulike.org/user/HEIRS/article/6426071
12. Nrf2 Regulates Antioxidant Gene Expression Evoked by Oxidized Phospholipids in Endothelial Cells and Murine Arteries In Vivo http://www.citeulike.org/user/HEIRS/article/6425259
13. Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells http://www.citeulike.org/user/HEIRS/article/1496816
14. Cigarette Smoking Blocks the Protective Expression of Nrf2/ARE Pathway in Peripheral Mononuclear Cells of Young Heavy Smokers Favouring Inflammation http://www.citeulike.org/user/HEIRS/article/6425199
15. Coenzyme Q10 deficiency in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardi. http://www.citeulike.org/user/HEIRS/article/6414392
16. TLR4 is Necessary for Hyaluronan-mediated Airway Hyperresponsiveness After Ozone Inhalation http://www.citeulike.org/user/HEIRS/article/6424875

Nrf2 as a Therapeutic Target for Stroke and Neurodegeneration

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity: "URL: Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity

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Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes.

Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes.: "URL: Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes.

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Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse

Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse: "URL: Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse

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Mitochondrial defects ‘drive beta-cell dysfunction in diabetes’

Dysfunction of the pancreatic beta cells – the primary defect underlying insulin resistance and Type 2 diabetes – is driven by abnormal mitochondrial function and morphology, Canadian researchers have discovered.

LINK

Abstract: Mitochondrial dysfunction and metabolic syndrome - looking for environmental factors

Lee, H. K. K., Cho, Y. M. M., Kwak, S. H. H., Lim, S., Park, K. S. S., and Shim, E. B. B. (2009). Mitochondrial dysfunction and metabolic syndrome - looking for environmental factors. Biochimica et biophysica acta. http://www.citeulike.org/user/HEIRS/article/6171518

Your Mother's High Fat Diet May Contribute To Your Impaired Liver Function as Adult Says New Study

Title: Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression

Summary: "Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis."


Citation: Bruce, K. D., Cagampang, F. R., Argenton, M., Zhang, J., Ethirajan, P. L., Burdge, G. C., Bateman, A. C., Clough, G. F., Poston, L., Hanson, M. A., McConnell, J. M., and Byrne, C. D. (2009). Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology, 9999(9999):NA+. http://www.citeulike.org/user/HEIRS/article/5917857

Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells

Title: Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells.

Summary: Saturated and unsaturated fats were studied to determine the effects of glucose metabolism and mitochondrial function. Palmitic acid and stearate decreased mitochondrial function which was determined by hyperpolarization and generation of ATP. They also decreased Akt activation by insulin. Unsaturated fat did not disturb mitochondrial function or glucose metabolism. This study shows that in muscle cells saturated FFA-induced mitochondrial dysfunction associated with impaired insulin-induced glucose metabolism


Citation: Hirabara, S. M., Curi, R., and Maechler, P. (2009). Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. Journal of Cellular Physiology. http://www.citeulike.org/group/6182/article/5843695

Saturated Fats, High-fat Diets and Coconut Oil -- No, There NOT that Good For You

The Real Facts About Coconut Oil --

If You HAVE Environmental Illness It May Not Be Good For You

There seems to be some misunderstanding about fats in general and environmental illness, so I thought I would provide some information to you and as a reader, if you have environmental illness of one sort or another the information in the paragraphs below pertain specifically to you.  First of all, part of the consequences of injury from environmental illness includes insulin resistance, damage from inflammation and endothelial dysfunction (Helyar) due to bioaccumulation and the chemicals effects on cellular function and signaling. Almost everyone in the US and Canada...in cities or the country that do not grow all their own food on organic farms have some levels of toxins stored in their body and the fat cells are most often, where they are stored. Arsenescu explains how dioxins and PCB both have been shown to increase and expand adipose tissue and therefore, there is significant potential for toxic exposures that lead to obesity, cardiovascular disease, diabetes and cancer (Rutkowski).  Yoshanari explains that the effects of toxins are still unclear but there is mounting evidence that toxicants can change the function/secretion of adipokines produced by adipocytes and have important roles in metabolic and endocine function. His research suggests that lipophilic toxicants in adipose tissue "activate the aryl hydrocarbon and the Nrf2 which increase detoxification but also may change the genetic expression of adipokines resulting in unexpected effect on tissue." Interestingly, animals that are AhR-/- do not gain weight in response to dioxin which suggest suppression of expression. (Arsenescu) Abdollahi and Rezg demonstrates subchronic effects of malathion exposure upsets glucose homeostasis and may induce diabetes through mechanisms including increased energy needed for detoxification and a decrease in paraxonase activity. Incidentally, Rezg's findings also show  some of the harmful effects of malathion can be aleviated with the addition of the polyphenol caffeic acid which increases acetylcholinesterase.

To some extent the effects of a high-fat diet, atleast in terms of changing gene expression, parallel those of the effects of toxic injury on adipocytes and both exacerbate the impact of each other. A "sedentary lifestyle and overeating are two conditions that are associated with weight gain and obesity that lead to insulin resistance. Insulin resistance is a condition where insulin has less than desired effects of disposal of glucose in the muscle and the improper suppression of glucose production in the liver.  Obesity and mitochondrial dysfunction are risk factors for insulin resistance and obese individuals have smaller mitochondria and exhibit compromised mitochondrial bioenergetic capacity. Insulin resistance also occurs with age, and a related defect in fatty acid oxidation has been identified." (Liang) Several conditions can influence the development of insulin resistance and sedentary lifestyles and overeating can be characteristic patterns of behavior of those who are ill. Researchers suspect there are a number of physiological consequences of bioaccumulation including the increase of inflammatory mediators that can lead to insulin resistance, for example, through increases in Tnf-a. Certain fats including those in coconut oil, like Tnf-a, can switch off important genes necessary for cellular metabolism including PGC-1a which may lead to a gradual shut-down of the mitochondria. Environmental influences like these may also explain the development of diabetes in adulthood. (Coghlan) Exercise, sedentary lifestyles and nutritional factors have all been demonstrated to regulate PGC-1a and regulate insulin sensitivity. Inflammation in the "fat" can also leak out and cause inflammation in the muscles surrounding them increasing insulin resistance.

Below is some general information related to fat which is important because insulin resistance is a risk factor for diabetes and diabetes is associated with bioaccumulation and obesity and environmental illness. One needs to understand the concept of triglycerides in addition to fat. Corcoran explains that "intracellular triglycerides are associated with diminished insulin sensitivity in skeletal muscle. This lipid accumulation is likely due to enhanced fatty acid uptake in the muscle coupled with diminished mitochondrial lipid oxidation. Excess fatty acids are esterified and either stored or metabolized to various molecules that may participate or interfere with normal cell signaling, particularly with insulin, mediated signal transduction and subsequently whole body glucose metabolism. Impaired insulin responsiveness if not managed, can lead to diabetes.  Chronic over-consumption of calories coupled with deleterious intakes of fats have been shown to increase the risk of insulin resistance." These statements become particularly important to those with chemical injury and environmental illness because inefficient mitochondria and inflammation makes the body more insulin resistant. Most of the studies already published on the health benefits of fats in coconut oil,as far as I can tell, are on healthy people that do not have chemical sensitivities and do not have uncontrolled oxidative stress and do not have diminished mitochondrial function and insulin resistance already present.

Here are some important facts and definitions to understand when it comes to fat: American Diabetes Association

The ADA recommends less than 7% of saturated fat per day for most people. The exact amounts truly depend on a variety of factors including age, physical activity etc. Most Americans get more than that and I would assume so do most Canadians.

• 
  
  
  Generally, saturated fat raises cholesterol. From what I can see from the research, there is not a lot of evidence of coconut doing so directly, even though the ADA says it might. Saturated fat is in meats, lard, butter etc. Palm, Palm Kernel and Coconut oil are saturated vegetable oils. The have a different molecular formula from traditional longer-chain hydrogenated fats and are made of medium chain fatty acids. Trans fat is what is called hydrogenated oils and we know them as the oils that are more solid and found in snack food that are labelled as such, stick margarine, shortening and fast food.
  
  
  
• 
  
  
  Monounsaturated fats are those that are the more healthy fats and are sometimes called seed oils and may include canola, avocado, etc.
  
  
  
• 
  
  
  Polyunsaturated fats include corn oil, sunflower oil, cottonseed oil, etc.
  
  
  
• 
  
  
  Omega - 3 -- in fish and some plants, ie flax.
  
  
  
• 
  
  
  Cholesterol -- you body makes it and it comes from your diet.
  
  
  

Note: Coconut oil does not provide a good source of essential fatty acids so it is not a good replacement for sources that do. (Hargrave)

You may have noted some of the recent positive reports that have been published in the media lately not just about coconut oil but also medium chain fatty acids. The first one is they may help prevent diabetes better than long-chained fatty acids. Yes, this may be true if the results of the study are correct. However, this is not the full story. When doing health research or presenting health information to people that are already ill, one needs to dig a little deeper. Lets take a look at the fatty acid profile of coconut oil. By the way, I looked at the label on jars I bought --90% or more of the fat in coconut oil is saturated fat. It does not matter if you buy organic, virgin or extra-virgin coconut oil most of the fat in coconut oil is saturated fat. Also, in case your interested according to most of what I read there is little or no difference in virgin or extra-virgin coconut oil. It is labelled like this to be more marketably friendly so it can more favorably compared to olive oils. Virgin coconut oil is regarded as the highest quality coconut oil and is preferred for food preparation and home medicinal use. 18 members of Asian and Pacific Coconut Community (APCC) make about 85% of the coconut oil produced. (Wipedia)

The Natural Medicine Comprehensive Database has determined there is insufficient evidence that coconut oil can be used effectively to treat the flu, candida, the common cold, HIV/AIDS, preventing maternal HIV transmission, gonorrhea, candida infections, etc. and the safety for use as a medicinal is not known. George Mateljan is an expert on alternative nutrition and started one of the largest organic health food companies in this country. He has written several books about nutrition and his last book, the World's Healthiest Foodsis almost 900 pages and full of well-researched information. It was published in 2007 and even now is considered somewhat outdated because of the advances in research in the study of lipomics. If you want a good resource about nutrition and how to cook good food, it is definitely worth a gander and if you like, a purchase. This is what he writes about coconut oil. "Coconut oil is mostly saturated fat and as it turns out, not all saturated fat is bad for you. Of the saturated fat found in coconut oil, only 9% is made of long-chained fatty acid which are associated with heart disease. (This may be true but there are lots of other health conditions that can be exacerbated by fat!) Most of the fat in coconut oil is lauric acid which has a reputation of being heart-healthy. (Yes, but as you will see, may not be good for MCSers) About 30% of the medium-chain triglycerides can be taken up from the digestive tract and into the blood without metabolic work. Since coconut oil is mostly medium-chain triglycerides it can provide the same benefit. (I would expect if a person has some types of intestinal dysfunction, it could cause diarrhea or a similar malady. It might be beneficial to ask a physician about this!)

I (meaning Mr. Mateljan) have noticed that coconut oil is well promoted on the Internet with many claims for its health benefits. Mostly notably for its antiviral activity. But from the research I have seen, most of the conclusions are preliminary given there is not that much research published on the subject and that is done mostly on the individual components. But it looks pretty good for coconut oil but I (meaning he) will look at the research as it comes in." This is his opinion and again, I have to say that at the time it was published this may have been true. However, there are numerous discoveries on lipid regulation that have been made that he may not have been aware of or are newer than when the book was published and/or written. Also, I am sure he does not research with a perspective of someone with environmental illness because he is a chef, entrepreneur and a nutritionist. The statements in his book are also published on his website and as far as I can tell from what I read, what the website says and what my book says is no different. Again, the name of the book is the World's Healthiest Foods by George Mateljan.

Garvan notes a typical Western diet contains 40% saturated fat, 40% monounsaturated fat, 20% polyunsaturated fat of which most are omega-6 not omega-3. Thus high-saturated fat diets are contributory to diabetes and obesity.  In addition, because there are no essential fatty acids in coconut oil, a diet in saturated fat usually is essential fatty acid deficient in linoleic acid an omega-6 fatty acid and alpha-linolenic, an omega-3 fatty acid. (Best)

This is the FA Profile of Coconut Oil: Wipedia

Fatty Acid	Saturation	Carbons	Percent
Caproic	Saturated	6	0.5
Caprylic	Saturated	8	7.8
Capric	Saturated	10	6.7
Lauric	Saturated	12	47.5
Myristic	Saturated	14	18.1
Palmitic	Saturated	16	8.8
Stearic	Saturated	18	2.6
Arachidic	Saturated	20	0.1
Oleic	Monounsaturated	18	6.2
Linoleic	Polyunaturated	18	1.6
Coconut oil contains approximately 92.1% saturated fatty acids, 6.2% monounsaturated fatty acids, 1.6% polyunsaturated fatty acids. The above numbers are averages based on samples taken. Numbers can vary slightly depending on age of the coconut, growing conditions, and variety.

As you can see from the table above, the most of what is contained in coconut oil is lauric acid, myristic and palmitic saturated fats. First, let me draw your attention to lauric acid. The amount of lauric acid in coconut oil is 47.5% according to the chart above. 3dChem.com describes lauric acid as the main oil in palm oil and coconut oil and that it has antimicrobial properties. It also says that lauric acid is slightly irritating to mucous membranes and is used in soaps and shampoos. Sodium lauryl sulfate is the most common lauric-acid derived compound used for this purpose. Yes, SLS is used in food and several different types of food from regular table food to pharmaceuticals. Lauric acid can react with solvents like water, as well as fats, which is why SLS is used in shampoo. As most people already know many MCSers are very sensitive to SLS. Other studies have shown that it can cause sensitivities in people that take medication made with SLS. In skin, SLS has been demonstrated to inhibit lipid-metabolizing enzymes including PPAR-alpha and PPAR-gamma which if you have read my blog can already be down-regulated by Tnf-a. (Torma) Tnf-a can be produced as a consequence of the stress response and toxic injury and therefore may be quite prevalent in environmental health conditions. One of the functions of PPAR-gamma includes regulating insulin sensitivity (Chatterjee) which is mediated by adiponectin that reduces insulin resistance. Adiponectin also is down-regulated by Tnf-a and has been shown in a study to be down-regulated by the high-fat of coconut oil (Bueno). Another study shows, SLS mediates skin barrier injury after 5-weeks and makes it more sensitivity to external stress. Considering that lauric acid is an irritant and is found in SLS....one can assume that it may be the agent at least in part that causes the irritation from SLS in people who are already sensitive to different "agents". Another study shows ceramides are also increased by SLS and ceramides from mitochondrial dysfunction down-regulate Nrf2 so one may be able to make a connection with further information and research. Nrf2 can be impaired for a number of reasons including age and genetics and makes one more susceptible to oxidative stress and susceptible to aberrant inflammation. It is also down-regulated by hyperglycemia (high blood sugar) and high-fat diets. Now, there is no specific research that says that lauric acid is the only thing in SLS as far as I can tell that may be an irritant, but the fact that it is in there and if a person is sensitive or thinks they may be sensitive to SLS, it might be a good idea to stay away from it. Not all MCSers are sensitive to SLS, but I am one and therefore, no matter how useful it is for cooking, I would never think about using it. I would rather be safe now than sorry later because my reactions can occur quickly or be delayed by hours or even days.

Many studies note that medium-chained fatty acid do not result in the accumulation of fat in muscle and the liver and from all accounts medium-chained fatty acids are better healthwise than long ones. But there are a few things one must consider since the American diet consists of 40% saturated fat which is 33% more than is recommended. In the literature, there seems to be some debate about the effect of long-chained fatty acids on mitochondrial function. Schrauwen says they have little effect and others say they may impair mitochondrial function by example, by opening of the transition pore that increases mitochondrial swelling causing cell death. (Wiekowski, Korge) As noted above, a recent claim was made that short-chain FA can prevent diabetes. (Medical News Today) Well, in actuality the study says it can preserve insulin action in muscle and adipose tissue. Which is great if you have healthy adipose tissue and muscle --and as we have shown people with environmental illness probably do not! In addition, it says that it does increase steatosis (fatty liver) and insulin resistance in the liver and there are alot of mitochondria in liver cells. (Turner) Many people that have been exposed to toxicants have injured livers in addition to impaired functioning of the mitochondria. Personally, I really do not want my liver fatty because it has to last a really long time...well, hopefully anyway! Most people are uneffected by fatty liver but then there are others where the condition results in elevated inflammation and scarring and at its worst, liver failure. (Mayon Clinic) If one reads that coconut oil gives an energy boost the author may be extrapolating from the fact that fats provide energy which I have to argue at least to a point. It may be true but it may not be true in people with mitochondrial disease or dysfunction. Garvan explains a benefit of medium-chain fatty acids is they are small enough to cross the membrane and supply energy to the mitochondria. That is all fine and good if the mitochondria are working well but alot of excess energy is not so good if they aren't. Mitochondrial function naturally generates free radicals and an increase in them may generate an increase in oxidative stress that may impair it further and may induce other aberrant signaling the least of which may include drastic changes in mood. There is evidence the activity of PKC is "defective" in diabetes and obesity and as a result may lead to altered glucose transport. (Corcoran) New research has implicated PKC signaling in fatty-acid induced insulin resistance and others identify PKC involvement in connection with lead poisoning and PTSD although I have yet to follow up on the specifics. Many people including those with environmental illness have stored levels of lead and other metals that are released under physiological stress conditions. Many conditions including exposures may result in a hyperglycemia response, so alterations in PKC signaling is something one must consider. You might recall a recent report showed a higher incidence of metabolic syndrome in those with PTSD. PKC signaling may offer a possible explanation and then again, maybe it doesn't.

Palmitic acid is also known as palmitate which is the salts or esters of palmitic acid. (Wipedia) It is one of the most common fatty acids in plants and animals and is number 3 on the list of fatty acids in coconut oil. It too shows no hypercholesterolemic effects from what I initially saw from the research. But that does not mean it can not in certain people or that it does...it just means I did not find it. Except and this is a big except, in the presence of trans fat which unfortunately, is still a big part of many people's diet even though many try to avoid it.   Eli Lilly produced a report that indicates that palmitate causes down-regulation of PGC-1a which is an important requirement for mitochondrial biogenesis which the end result is energy. It is safe to assume that down-regulating PGC-1a can be more detrimental to cells that already have less mitochondria that function abnormally and are insulin resistant. (Otto) eNOS can also be deficient in PGC-1a deficient cells which may increase the risk for endothelial dysfunction that has been implicated as a factor in a number of environmental illnesses.  Bonnard's studies suggest that high-fat, high-sugar diets can induce glucose intolerance after 1 month and a longer intervention with the same diet induced diabetes with altered mitochondrial biogenesis, structure and function and concludes that insulin resistance precedes mitochondrial dysfunction in diet-induced diabetes. (Bonnard)  Schrauen explains that palmitate, myristate and stearate do activate the NF-kappaB in muscle cells and since if one refers back to the chart above those three acids equals almost 30% of the saturated fat in cocnut oil. NF-kappaB may activate inflammatory processes which some called the "inflammatory cascade" and is implicated as an inflammatory marker in environmental illness. In people with lower Nrf2, NF-kappaB is a concern because Nrf2 normally is responsible for regulating it.

A just released paper indicates that palmitic acid changes brain chemistry in a "relatively short time" and tricks the brain into not realizing when one is full from eating. It does this by making the brain unresponsive to signals from leptin and insulin and therefore may cause one to overeat. (US News) This may contribute to the "expanding adipose tissue" problem and more inflammation we mentioned in the first paragraph. Now, granted palmitic acid makes up only 8% of the total fat content. If your like me, I do not want to be exposed to anything that changes my brain chemistry anymore that it has been already. At least that is, if I can avoid it. I have enough problems with sickness syndrome and brain fog! Palmitic acid has been demonstrated to cause a 75% increase in the expression of Tnf-a and a 75% decrease in Il-10 in adipocytes and Tnf-a is associated with environmental illness and causes insulin resistance and inhibits PGC-1a in vitro cardiac cells. (Palomer) (The increase in Tnf-a may explain some of the weight loss seen in some studies considering that Tnf-a causes cachexia and weight loss. Il-10 is associated with preventing lipid-induced insulin resistance, reducing the severity and length of sickness syndrome and modulating HO-1. All of these factors have been implicated as possible factors in environmental illness. (Bradley) Yamauchi shows that insulin resistance in lipoatrophy can be reversed with expression of both adiponectin and leptin but only partially by either leptin or adiponectin alone. (Yamauchi) In other words, there may be instances that if one or the other of these genes are down-regulated then they may not be able to reverse insulin resistance if already present. Generally, high-fat diets are associated with impaired working memory and hippocampal morphology in animals. (Granholm)

Two important notes about the issues above, one needs to be careful when drawing conclusions about the health aspects of a population in comparison to another. If one population does not eat like another, live like another, work and exercise like another, have the same cultural problems, the same genes, and in this case, share the same disease or health condition it may lead a person to make conclusions that are inaccurate. Most indiginous populations, especially those isolated by geography are not effected by the same environmental influences modern societies are and therefore the aspects of their environmentally-related health conditions are different. I have read what is printed on "more popular" websites and also have read cultural graduate theses and there is some contradiction of the health effects of medium chain high-fat diets in different indiginous population studies. I am not saying comparison studies are not important but the more similar the cultures are the more valuable the data. Here are are few important things one might consider in a population study on fat. Are there other factors such as there are in this case, in the diet or lifestyle that may be offsetting the negative effects of a high-fat diet? Have their bodies adapted to their circumstances over time better than other populations? A recent study has demonstrated that the anti-inflammatory effects of vitamin E may be associated with certain Tnf-a and it has been suggested that the positive benefits of coconut oil are that it is a good source of vitamin E.  Could up-regulated or down-regulated genes be altering the expression of proteins or is there a gene polymorphisms in the population being studied that makes them more adaptable to handle a negative influence? Are there comfounding factors that are increasing the health or inhibiting the effects such as more or lack of exercise or the use or no use of trans fat? As you can see from what was written above about the studies from palmitic acid in junk food and coconut oil down-regulating adiponectin, food can change the expression of genes quite quickly and researchers have no idea how long the effects can last. Is it possible these changes can become permanent on a population that has not fully "adapted" to them.  Maybe, maybe not. It would be my guess no one will say it can not happen because no one really knows for sure. There is now a whole field of research that explores how changes in gene expression is passed down to the next generation when there is no change in the DNA. Twenty years ago, researchers did not believe epigenetic influences could happen either.  

Environmental illness development is largely due to poor (I use this term loosely) diet, lifestyle, and exposures to toxic influences like chemicals and their influence on genetic expression and numerous other factors including bad decisions and choices.  In addition, scientists  are well aware toxicants can can up-regulate or down-regulate cellular receptors or interact with each differently and may lead to altered cell functions. There are thousands of chemicals now on the market that have the potential to do it. From a political and policy-making standpoint, the problem is how one goes about deciding which ones to to start testing first, who is gonna test them and what standards will be used to test them and also, who is gonna pay for it and how to deal with the economic fall-out afterward! Finally, making health decisions is in the end, a personal one and it is only that person, or mostly so, who has to live or not live with the consequences. Using coconut oil for cooking is still of benefit for one person because it does not produce the levels of aldehydes and does not turn rancid like other oils. But it may not be a wise choice for another who has a sensitivity to it or one of the chemicals in it. On the other hand, detoxification of aldehydes is often limited in environmental illness and therefore, cooking with coconut may be a better option for someone with one environmental illness compared to another person with another environmental illness.On the other hand, in many cases because of the nature of injury and inflammation in environmental illness, limiting fat should be of benefit to most. Unless of course, medical tests show a deficiency. Either way there are good lab tests available that can determine a person's fat and triglyceride status and a physician is more than qualified to discuss the topic.

 

 

 

 

 

Sonne, C., Fonfara, S., Dietz, R., Kirkegaard, M., Letcher, R., Shahmiri, S., Andersen, S., and Møller, P. (2007). Multiple cytokine and acute-phase protein gene transcription in west greenland sledge dogs (canis familiaris) dietary exposed to organic environmental pollutants. Archives of Environmental Contamination and Toxicology, 53(1):110-118. http://www.citeulike.org/user/HEIRS/article/1447133

Arsenescu, V., Arsenescu, R. I., King, V., Swanson, H., and Cassis, L. A. (2008). Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. 116(6). http://www.citeulike.org/user/HEIRS/article/5792101

Specific Types of Fat. American Diabetes Association. Retrieved on September 16, 2009.

Turner, N., Hariharan, K., TidAng, J., Frangioudakis, G., Beale, S. M., Wright, L. E., Zeng, X. Y., Leslie, S. J., Li, J.-Y., Kraegen, E. W., Cooney, G. J., and Ye, J.-M. (2009). Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species-dependent: Potent tissue-specific effects of medium chain fatty acids. Diabetes. http://www.citeulike.org/user/HEIRS/article/5792208

(2009). How coconut oil could help reduce the symptoms of type 2 diabetes. Medical News Today. http://www.citeulike.org/user/HEIRS/article/5793232

Coconut Oil. Wipedia. Retrieved on September 16, 2009.

Tasty Foods Send Signal to Brain to Keep Eating. US News. Retrieved on September 16, 2009.

Fatty Liver. Wipedia. Retrieved on September 16, 2009.

Keith Ott, O., Jack Dempse, Y., Richar, D., Beckman, N., and Anne Reifel Mille, R. Aicar reverses the effect of palmitate on metabolic gene expression and mitochondrial number in muscle cells and adipocytes. http://www.citeulike.org/user/HEIRS/article/5793413

Bradley, R. L., Fisher, F. F., and Maratos-Flier, E. (2008). Dietary fatty acids differentially regulate production of tnf-alpha and il-10 by murine 3t3-l1 adipocytes. Obesity (Silver Spring, Md.), 16(5):938-944. http://www.citeulike.org/user/HEIRS/article/5791246

Törmä, H., Geijer, S., Gester, T., Alpholm, K., Berne, B., and Lindberg, M. (2006). Variations in the mrna expression of inflammatory mediators, markers of differentiation and lipid-metabolizing enzymes caused by sodium lauryl sulphate in cultured human keratinocytes. Toxicology in vitro : an international journal published in association with BIBRA, 20(4):472-479. http://www.citeulike.org/user/HEIRS/article/5793447

Helyar, S. G., Patel, B., Headington, K., El-Assal, M., Chatterjee, P. K., Pacher, P., and Mabley, J. G. (2009). Pcb-induced endothelial cell dysfunction: role of poly (adp-ribose) polymerase. Biochemical pharmacology. http://www.citeulike.org/user/HEIRS/article/5041282

Chatterjee, V. K. K. (2001). Ppar gamma and human insulin resistance. In Society for Endocrinology Annual Meeting 2001. BioScientifica. http://www.citeulike.org/user/HEIRS/article/5793459

Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., Ezaki, O., Akanuma, Y., Gavrilova, O., Vinson, C., Reitman, M. L., Kagechika, H., Shudo, K., Yoda, M., Nakano, Y., Tobe, K., Nagai, R., Kimura, S., Tomita, M., Froguel, P., and Kadowaki, T. (2001). The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Medicine, 7(8):941-946. http://www.citeulike.org/user/HEIRS/article/5793464

Keith Ott, O., Jack Dempse, Y., Richar, D., Beckman, N., and Anne Reifel Mille, R. Aicar reverses the effect of palmitate on metabolic gene expression and mitochondrial number in muscle cells and adipocytes. http://www.citeulike.org/user/HEIRS/article/5793413

Corcoran, M. P., Lamon-Fava, S., and Fielding, R. A. (2007). Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr, 85(3):662-677. http://www.citeulike.org/user/HEIRS/article/5791465

Törmä, H. and Berne, B. (2009). Sodium lauryl sulphate alters the mrna expression of lipid-metabolizing enzymes and ppar signalling in normal human skin in vivo. Experimental dermatology. http://www.citeulike.org/user/HEIRS/article/4787882

Harrison, K. (2007). Lauric acid @ 3dchem.com. http://www.citeulike.org/user/HEIRS/article/5793491

Turner, N., Hariharan, K., TidAng, J., Frangioudakis, G., Beale, S. M., Wright, L. E., Zeng, X. Y., Leslie, S. J., Li, J.-Y., Kraegen, E. W., Cooney, G. J., and Ye, J.-M. (2009). Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species-dependent: Potent tissue-specific effects of medium chain fatty acids. Diabetes. http://www.citeulike.org/user/HEIRS/article/5792208

Kim, E., Kim, S., Nam, G. W., Lee, H., Moon, S., and Chang, I. (2009). The alkaline ph-adapted skin barrier is disrupted severely by sls-induced irritation. International journal of cosmetic science, 31(4):263-269. http://www.citeulike.org/user/HEIRS/article/5117257

Mateljan, George.The World's Healthiest Foods. Essential Guide for the Healthiest Way of Eating. George Mateljan Foundation. 2007. pg 55.

Sepp, Dennis, PhD. Sodium Lauryl Sulfate - The Straight Story. Retrieved on September 16, 2009.

Bueno, A. A. A., Oyama, L. M. M., de Oliveira, C., Pisani, L. P. P., Ribeiro, E. B. B., Silveira, V. L. F. L., and Oller do Nascimento, C. M. M. (2008). Effects of different fatty acids and dietary lipids on adiponectin gene expression in 3t3-l1 cells and c57bl/6j mice adipose tissue. Pflügers Archiv : European journal of physiology, 455(4):701-709. http://www.citeulike.org/user/HEIRS/article/5780642

Granholm, A.-C. C., Bimonte-Nelson, H. A., Moore, A. B., Nelson, M. E., Freeman, L. R., and Sambamurti, K. (2008). Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat. Journal of Alzheimer's disease : JAD, 14(2):133-145. http://www.citeulike.org/user/HEIRS/article/5780645

Palomer, X., Alvarez-Guardia, D., Rodriguez-Calvo, R., Coll, T., Laguna, J. C., Davidson, M. M., Chan, T. O., Feldman, A. M., and Vazquez-Carrera, M. (2009). Tnf-alpha reduces pgc-1alpha expression through nf-kappab and p38 mapk leading to increased glucose oxidation in a human cardiac cell model. Cardiovasc Res, 81(4):703-712. http://www.citeulike.org/user/HEIRS/article/4594676

Bonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M. A., Morio, B., Vidal, H., and Rieusset, J. (2008). Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. The Journal of clinical investigation, 118(2):789-800. http://www.citeulike.org/user/HEIRS/article/3152490

Rutkowski, J. M., Davis, K. E., and Scherer, P. E. (2009). Mechanisms of obesity and related pathologies: The macro- and microcirculation of adipose tissue. FEBS Journal, 9999(9999). http://www.citeulike.org/user/HEIRS/article/5795717

Nonalcoholic fatty liver disease. Mayo Clinic. Retrieved on September 16, 2009.

Wieckowski, M. (2000). Long-chain fatty acids promote opening of the reconstituted mitochondrial permeability transition pore. FEBS Letters, 484(2):61-64. http://www.citeulike.org/user/HEIRS/article/5797786

Korge, P., Honda, H. M., and Weiss, J. N. (2003). Effects of fatty acids in isolated mitochondria: implications for ischemic injury and cardioprotection. Am J Physiol Heart Circ Physiol, 285(1):H259-269. http://www.citeulike.org/user/HEIRS/article/5797780

Belisle, S. E., Leka, L. S., Delgado-Lista, J., Jacques, P. F., Ordovas, J. M., and Meydani, S. N. N. (2009). Polymorphisms at cytokine genes may determine the effect of vitamin e on cytokine production in the elderly. The Journal of nutrition. http://www.citeulike.org/user/HEIRS/article/5800741

Hargrave, K. M., Azain, M. J., and Miner, J. L. (2005). Dietary coconut oil increases conjugated linoleic acid-induced body fat loss in mice independent of essential fatty acid deficiency. Biochimica et biophysica acta, 1737(1):52-60.  http://www.citeulike.org/user/HEIRS/article/5800784

Lauric acid. RX List. Retrieved on September 17, 2009.

Yoshinari, K., Okino, N., Sato, T., Sugatani, J., and Miwa, M. (2006). Induction of detoxifying enzymes in rodent white adipose tissue by aryl hydrocarbon receptor agonists and antioxidants. Drug Metab Dispos, 34(7):1081-1089. http://www.citeulike.org/user/HEIRS/article/783432

Liang, H. and Ward, W. F. (2008). Pgc-1: a key regulator of energy metabolism. http://www.citeulike.org/user/HEIRS/article/5805611

Olive Chemistry- The Olive Oil Source. Retrieved on September 17, 2009

Nicholls, S. J., Lundman, P., Harmer, J. A., Cutri, B., Griffiths, K. A., Rye, K.-A. A., Barter, P. J., and Celermajer, D. S. (2006). Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function. Journal of the American College of Cardiology, 48(4):715-720. http://www.citeulike.org/user/HEIRS/article/5805848

Coghlan, A. (2009). Fat reprograms genes linked to diabetes. NewScientist. http://www.citeulike.org/user/HEIRS/article/5831238

Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme, Vol. 33, No. 5. (October 2008), pp. 843-862.

Abdollahi, M., Donyavi, M., Pournourmohammadi, S., and Saadat, M. (2004). Hyperglycemia associated with increased hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase in rats following subchronic exposure to malathion. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 137(4):343-347.  http://www.citeulike.org/user/HEIRS/article/2988987

Rezg, R., Mornagui, B., El-Fazaa, S., and Gharbi, N. (2008). Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity. Toxicology, 250(1):27-31. http://www.citeulike.org/user/HEIRS/article/5831958

Biological and Behavioral Factors: Increasing the Risk for Environmental Disease Development!

Background: Chen explains, "GSK3b is like an on/off switch for the detoxification system Nrf2. Endoplasmic reticulum stress can be caused by consistent and long-term activation of nociceptors as well as, abnormal dopamine flux by genetic alterations or environmental insults like the abuse or use of certain drugs. Dopamine-generated ER stress can activate the GSK3b response through PP2A that leads to neuronal death. This is the type of neuronal death that has been implicated in the neural degeneration seen in Parkinson's disease. Indications of ER dysfunction include unfolded protein response and may also activate the NF-kappa B inflammatory pathway. Other studies have shown it may be important in acute brain injury and other chronic degenerative diseases including Alzheimer's. GSK3b activity has been shown to be regulated by ER stress, oxidative stress, heat shock and and hyperosmosis."

• GDNF and BDNF provide protection against GSK3b but may be down-regulated in some instances of environmental illness.
• Inhibition of PP2a result in the inhibition of GSK3b activation leading to apoptosis (programmed cell death).
• Ceramide-dependant activation of PP2a leads to the downregulation of Nrf2. (Hagan)
• (R)-alpha-lipoic acid (LA) has been shown to positively regulate the gene expression of Nrf2 which is the basis of Tory Hagan's research, in addition to PP2A activity, at the Linus Pauling Institute at Oregon State University. Nrf2 up-regulates heat shock protein HO-1.
• PP2a increases parallel increases in a-synuclein. (Peng)

Conclusions: Nrf2 is a modulator of the effects of gasoneurotransmitters through HO-1. Its impairment can not only result in susceptability to the effects of CO, NO and H2S but also the effects of catecholamines (ie. dopamine) that are activated by stress as part of the stress response. Long-term continuous activation of endoplasmic reticulum stress with impairments in Nrf2 can lead to environmentally induced conditions such as neurodegenerative conditions and brain injury as well as other inflammatory consequences including mitochondrial deficiency. Muscarinic receptors upregulate Nrf2 and Chaudhuri demonstrates the increase or decrease of binding of pesticides to the muscarinic receptor depends on the type of pesticide and greatly influences the toxicity of the pesticide. In his study, he showed paraquat's toxicity was greater. In addition, agricultural products may be contaminated with other agents or include "inert" ingredients that increase their toxicity by negatively influencing the expression of Nrf2 and/or its downstream targets. Other environmental influences may include nutrition (ie. obesity, malnutrition and high fat diets), mitochondrial disease, genetic mutations in the dopamine transporter (DAT) or DJ-1, or those in Nrf2, contaminants like dioxin and endotoxin that activate the AhR all enhance toxicity and risk for environmental disease.

Click for a more detailed list:

• biological factors that are directly related to Nrf2 signaling are may be mentioned within the body of blog text

Citations: Original Document