Low Grade Endotoxemia And Inflammatory Diseases

Amazoniac

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Members that don’t post 30 analyzed studies on a 2-minute interval to avoid getting distracted by questions about an itchy crotch;
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Causes and consequences of low grade endotoxemia and inflammatory diseases. - PubMed - NCBI

“Mice fed a high fat diet show a decrease in the expression of proteins associated with the formation of the tight junction (33). High fat diets have also been shown to cause an increase in glucose tolerance, increased levels of macrophage infiltration in adipose tissue and markedly higher levels of pro-inflammatory markers. A knockout of CD14, a key LPS signaling molecule, primarily expressed on macrophages and neutrophils who are responsible for recognition and phagocytosis of LPS, reversed these findings (9, 33). Additional environmental exposure to bacteria plays a necessary role in the creation of the chronic inflammatory state. The gut microbiota also plays a major role in contributing to disease. Mice bred in a sterile facility also fed with a high fat diet did not exhibit any of the symptoms of disease, but upon the introduction of bacteria from other mice characteristic metabolic endotoxemia ensued (34). In summary, the gut microbiota changes and high fat feeding cause a significant increase in circulating levels of endotoxin. Collectively, these factors contribute to low-grade inflammation.”

“In the mouth, bacteria are capable of forming thick biofilms that are very resistant to antiseptics, antibiotics, and mechanical removal. Several of the bacteria associated with this disease are Gram negative in nature, including the Porphyromonas species. These bacteria have routine and easy access to the circulatory system during mechanisms that can cause lesions like the chewing of food or during teeth cleaning. The exact mode of entry into circulation has not been well defined, but studies have shown that individuals with severe periodontitis have elevated serum levels of LPS (41, 42).”

“Several studies were able to show that elderly individuals have significantly elevated levels of circulating endotoxin (~3-11 pg/mL) (49-51). The combination of immune dysfunction and increased instances of chronic inflammatory diseases suggest that elevated levels of circulating endotoxin could be the underlying culprit.”

“It is also now widely accepted that adipose tissue is not only a storage cell for lipid, but is a highly metabolic, highly secretory tissue capable of influencing the inflammatory state of the host. Elevated plasma endotoxin levels, as well as the secretion of pro-inflammatory cytokines such as interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and TNFα by both adipose tissue macrophages (ATMs) and adipocytes themselves are now being recognized as risk factors for T2DM (29, 33, 55).”

“To add to the complexity of the IR development, the interactions and balance between anti-inflammatory, catabolic programs with the pro-inflammatory programs of activated TLR4 in innate immune cells and adipocytes play a major role in determining the insulin sensitivity of an individual. Co-repressor activity plays a major role in the relationship between TLR inflammatory transcription factor activation and nuclear receptor activity responsible for metabolic programs. In adipose tissue and macrophages, the expression of PPARs promotes an M2 polarization and is responsible for maintaining the basal anti-inflammatory tone of adipose tissue via promoting the co-repression of pro-inflammatory genes through co-repressors nuclear receptor corepressor 1 or 2 (NCoR). However, in our studies and in others, PPAR expression is inhibited after TLR4 stimulation by LPS, and complete knock out of this nuclear receptor promotes inflammation and IR (9).”
Basically “..demonstrating the necessity for inflammation in the presence of obesity for the development of IR.”

“Additionally, increase in intracellular lipids can cause direct lipotoxicity to cells not normally accustomed to high lipid accumulation and oxidative stress caused by increased flux of lipids going through β-oxidation can contribute to the activation of IR through mitochondrial and ER [Emergency RoI mean, Endoplasmic Reticulum, related to protein synthesis, modification, transport, etc] stress (31).”

“Recently, adipose tissue has begun to be recognized as not only a highly metabolic tissue, but also one that is highly capable of influencing an individual’s inflammatory profile (53, 56, 60). Adipose tissue is composed of several fractions: the adipocytes themselves and the stromal vascular fraction (SVF) which contains red blood cells, endothelial cells, and macrophages (46). In the obese state, the increased amount of circulating FFAs in combination with the increased levels of circulating endotoxin, and the hypoxic state in adipocytes toward the center of the fat tissue is a substantial stimulus for inflammation.”
In other words, it’s not neglected that obesity by itself can set problems, including inflammation; apparently one reinforces the other..

“Additionally, lipid accumulation in the liver of obese individuals stimulates the release of pro-inflammatory mediators IL-1β, IL-6 and TNFα from hepatocytes, which then systemically can provide an inflammatory environment contributing to and exacerbating the developing inflammation (31).”

“As mentioned previously, the ingestion of a HFD has been theorized to contribute to the movement of LPS across the gut mucosa and into circulation. Consumption of HFD also allows for the increase of circulating fatty acids (FAs), which together with LPS may synergize the activation of TLR4, which has been shown to be up-regulated in macrophages in conditions of obesity (49). The activation of the TLR4 pathway subsequently leads to the induction of pro-inflammatory cytokines (53).”

“From another angle, the increase of FFAs in circulation also appears to activate adipocytes to secrete adipokines which stimulate macrophage migration to these tissues and influence polarization toward an M1 pro-inflammatory phenotype. These tissue macrophages subsequently become a potent source of pro-inflammatory cytokines, namely TNFα, IL-6 and IL-1β, ultimately resulting in the leakage of these cytokines into circulation.”

“In a study by Qin et. al., mice were injected intraperitoneally with a high dose of LPS (5mg/kg) (37). Plasma and tissue levels of TNFα rose quickly and subsided to similar levels as the control mice at 9 hours post injection. However, the protein levels of TNFα in the brain remained elevated up to 10 months post injection.” :ss

“We recently observed that low dose LPS as seen in low grade endotoxemia triggers an opposing effect toward PI3K [related to glucose metabolism and induction of pro but also anti-inflammatory mediators] (11). Instead of activating PI3K pathway and related anti-inflammatory effects, low dose LPS potently suppresses PI3K (11).”

“A study found that old mice were ten times more sensitive to endotoxin. Upon LPS challenge older mice exhibited an increase in TNFα, nitric oxide production, and mortality (93).”

“Studies published by Urbaschek in the 1970’s and 1980’s demonstrated a wide range in LPS sensitivity in the same cells derived from different species (95-97). In particular, it was reported that LPS sensitivity in Kupffer cells from guinea pig, hamster, mouse, and rat varied significantly (98). The gender of the individual challenged with LPS also affects one’s sensitivity to endotoxin (99). A study done on human volunteers was able to show that whole blood samples taken from males produced higher levels of pro-inflammatory cytokines like TNFα, IL-1β, IL-6, and IL-8 than their female counterparts (100).”

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Short version: it seems that low grade inflammation doesn't bother enough to scare the freegan to do something about it, so chronic problems start to develop slowly and relatively without symptoms. It also (apparently) doesn't trigger enough anti-inflammatory processes like acute inflammation does.
 
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