PROPENSITY TO HIGH FAT DIET-INDUCED OBESITY IN RATS IS ASSOCIATED WITH CHANGES IN THE GUT MICROBIOTA AND GUT INFLAMMATION.

Consumption of a high fat diet induces changes in the gut microbiota, but it is the development of inflammation that is associated with the appearance of hyperphagia and an obese phenotype.

"De La Serre, C. B. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., and Raybould, H. E. (2010). Propensity to high fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. American journal of physiology. Gastrointestinal and liver physiology."CiteULike: PROPENSITY TO HIGH FAT DIET-INDUCED OBESITY IN RATS IS ASSOCIATED WITH CHANGES IN THE GUT MICROBIOTA AND GUT INFLAMMATION.:

Immunosuppression in Environmental Illness By High Fat and Cytokines: Ameliorated By Green Tea Compound!?

A number of researchers now believe endotoxin from bacterial contaminants may be a pathway that leads to the development of chronic fatigue syndrome. In addition it has been determined that high-fat diets exacerbate inflammatory conditions by altering the TLR signaling pathway which contributes to the loss of suppression of inflammatory responses by regulatory T cells (tregs) after endotoxin injury. Many experts believe this loss of tolerance may play an important role in MCS which is a condition that exhibits symptoms that often appear autoimmune in nature. In the lungs, TLR signaling and other proteins induced by endotoxin lead to the increased expression of inflammatory mediators including IL-6 which suppress Treg expression resulting in loss of tolerance in the airway and increase inflammation. Incidentally, a very small amount of endotoxin can lower the threshold of immune reactions in some people and since humans do not live in sterile environments, we are consistantly exposed to endogenous and exogenous bacteria (and endotoxin) in the air we breath, the food we eat, the things we touch, etc.

EGCG, the compound in green tea, has been shown to provide relief in animal models of chronic fatigue syndrome and several studies show it may have several modes of action. Currently Tufts University is performing an in-depth analysis of EGCG and the preliminary results show EGCG has the capacity to regulate different subsets of T cells including those responsible for playing a role in the development of autoimmune-type disease such as tregs. In support of these preliminary findings, a few years ago, Yoneyama demonstrated EGCG can regulate IL-10 and does have substantial immunosuppressive properties.

Over the past few months I have written how humans and animals demonstrate sickness behavior and the related behavioral changes are consistent with many of the symptoms in CFS and may include fatigue, malaise, mood changes, decreased appetite, etc. Also, the severity of sickness syndrome is dependant on the production or absence of Il-10 which is necessary for Treg production. One inflammatory cytokine produced by endotoxin is Il-6 which has the ability to suppress Treg expression and is most often responsible for sickness syndrome behavior and the polyphenols in green tea inhibit the expression of it. Considering all of this, it makes sense the loss of Treg through abherrant signaling is a causal factor in the loss of tolerance and MCS, sickness syndrome and chronic fatigue syndrome. Lastly, Nrf2 along may influence and regulate Treg expression through HO-1 and Il-10.

CiteULike: A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury.: "Ma, X., Hua, J., Mohamood, A. R., Hamad, A. R. R., Ravi, R., and Li, Z. (2007). A high-fat diet and regulatory t cells influence susceptibility to endotoxin-induced liver injury. Hepatology (Baltimore, Md.), 46(5):1519-1529." http://www.citeulike.org/user/HEIRS/article/6496762
Duan, W., So, T., and Croft, M. (2008). Antagonism of airway tolerance by endotoxin/lipopolysaccharide through promoting ox40l and suppressing antigen-specific foxp3+ t regulatory cells. J Immunol, 181(12):8650-8659.
http://www.citeulike.org/user/HEIRS/article/3752381?show_msg=already_posted
Wu, D. Green tea egcg and t cell function in autoimmune inflammation.
http://www.citeulike.org/user/HEIRS/article/6496862
Yoneyama, S., Kawai, K., Tsuno, N., Okaji, Y., Asakage, M., Tsuchiya, T., Yamada, J., Sunami, E., Osada, T., and Kitayama, J. (2008). Epigallocatechin gallate affects human dendritic cell differentiation and maturation. Journal of Allergy and Clinical Immunology, 121(1):209-214. http://www.citeulike.org/user/HEIRS/article/6496680
Singal, A., Tirkey, N., Pilkhwal, S., and Chopra, K. (2006). Green tea (camellia sinensis) extract ameliorates endotoxin induced sickness behavior and liver damage in rats. Phytotherapy Research, 20(2):125-129.
http://www.citeulike.org/user/HEIRS/article/6496875

CiteULike: Effects of Coffee on Inflammatory Cytokine Gene Expression in Mice Fed High-Fat Diets

CiteULike: Effects of Coffee on Inflammatory Cytokine Gene Expression in Mice Fed High-Fat Diets: "Fukushima, Y., Kasuga, M., Nakao, K., Shimomura, I., and Matsuzawa, Y. (0000). Effects of coffee on inflammatory cytokine gene expression in mice fed high-fat diets. Journal of Agricultural and Food Chemistry, 0(0)."

 

 

Recommended:

• Giftcards from your favorite coffee store.  

High-fat diet impairs muscle health before impacting function

High-fat diet impairs muscle health before impacting function

Inflammatory Proteins and IL-10 in Obesity and Pathogenic Exposure: Implications for Sickness Syndrome and Fatigue!

Background: Sickness syndrome is a response to infection and inflammation and has been associated with production of Il-1b. Fatigue is a common symptom in environmental illness and may be a factor in sickness syndrome and recent studies provide evidence that activation of the Il-1 system may be a factor in causing the fatigue. Other studies demonstrate that Il-10 can modulate the severity of sickness syndrome through its interactions with HO-1 and other proteins such as BDNF.(Richwine) Richwine has also demonstrated that inflammatory processes increase in aged mice compared to adults. Meador has explained that IL-10 is associated with lower levels of inflammatory cytokines including Tnf-a, Il-1 and Il-6 in muscle and non-muscle.  The effects of aging on the expression of Il-10 would suggest alteration in SIRT1 or Nrf2/HO-1 and/or changes in expression of another gene that is effected by the aging process and high-fat diets.

New Research:
Title: Environmental and genetic factors influence the relationship between circulating Il-10 and obesity phenotypes.

Summary: "circulating IL-10 levels were associated not only with obesity status but also with genetic factors and with the exposure to environmental pathogens."

Citation: Bassols, J., Botas, P., Moreno-Navarrete, J. M., Delgado, E., Ortega, F., Ricart, W., and Fernandez-Real, J. M. (2009). Environmental and genetic factors influence the relationship between circulating il-10 and obesity phenotypes. Obesity (Silver Spring, Md.). http://www.citeulike.org/group/7167/article/5898650

Related Posts:

• Chronic Fatigue, Insulin Resistance, Il-10 and Sickness Syndrome
• CFS, Probiotics and Il-10
• Sickness Syndrome, CFS, Fibromyalgia, IL-10 and HO-1

Additional References:
Richwine, A. F., Sparkman, N. L., Dilger, R. N., Buchanan, J. B., and Johnson, R. W. (2009). Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide. Brain, behavior, and immunity, 23(6):794-802. http://www.citeulike.org/user/HEIRS/article/4710107
Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., and Johnson, R. W. (2005). Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. The FASEB Journal, 19. http://www.citeulike.org/user/HEIRS/article/4745254
Meador, B. M., Krzyszton, C. P., Johnson, R. W., and Huey, K. A. (2008). Effects of il-10 and age on il-6, il-1beta, and tnf-alpha responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. Journal of applied physiology (Bethesda, Md. : 1985), 104(4):991-997. http://www.citeulike.org/user/HEIRS/article/5488212

Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat.

Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat.

High Fat Diets Make One More Susceptible to Oxidative Stress and Environmental Illness!

Background:

• Obesity is also an important risk factor for a number of health conditions including diabetes and cardiovascular disease.
• Fatty liver disease is a condition where large amounts of fat accumulate in liver cells and is characteristic of metabolic syndrome. (Wipedia)

High fat diets decrease PGC-1a which is important for metabolic cellular processes, mitochondrial biogenesis and mitochondrial DNA synthesis. In addition, it decreases the expression of Nrf2 which is the master gene promoter that upregulates expression of genes important for the same process. The PGC-1a complex also controls another protein called Foxo3a which is an important modulator of aging. (Dong)

In addition to playing a role in redox homeostasis, Nrf2 modulates inflammatory mediators such as Tnf-a and MCP-1 and prevents lipid accumulation. Nrf2 is activated in response to toxicant injury and oxidative stress and is important for the detoxification of xenobiotics.
Tanaka's studies have shown the absence of Nrf2 increases susceptibility to toxicants including acetaminophen, hyperoxia, benzopyrene (found in smoke). He demonstrated that Nrf2 has important lipid metabolism and that feeding a high fat diet in the short term reduces Nrf2. He notes, other studies have shown long-term feeding of high fat diets increases Nrf2 and suggests this is an adapative response to oxidative stress induced by chronic fat accumulation. Generally, animals with lower Nrf2 present with elevated cholesterol levels and lower levels of Nrf2 results in the inability to prevent lipid accumulation, absence leads to greater retention of lipids in the liver (fatty liver disease) and greater oxidative stress including, oxidative stress in the mitochondria and the endoplasmic reticulum. Interestingly, Tanaka found that PGC-1a is reduced in high-fat diets but not in Nrf2 null mice which indicates the down-regulation of PGC-1a is dependant on Nrf2.

Summary: High fat diets reduce mitochondrial biogenesis, increases the likelihood for toxicant bioaccumulation and their overall toxic effects, increases oxidative stress, contributes to fat accumulation and obesity and impairs liver function which is an important organ for detoxification.

Dong, F., Li, Q., Sreejayan, N., Nunn, J. M., and Ren, J. (2007). Metallothionein prevents high-fat diet–induced cardiac contractile dysfunction role of peroxisome proliferator–activated receptor
coactivator 1 and mitochondrial biogenesis. 56(9):2201-2212. http://www.citeulike.org/user/HEIRS/article/5724999
Tanaka, Y., Aleksunes, L. M., Yeager, R. L., Gyamfi, M. A., Esterly, N., Guo, G. L., and Klaassen, C. D. (2008). Nf-e2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J Pharmacol Exp Ther, 325(2):655-664. http://www.citeulike.org/user/HEIRS/article/4788030