2013
DOI: 10.1371/journal.pone.0063983
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Effect of Lipopolysaccharide on Inflammation and Insulin Action in Human Muscle

Abstract: Accumulating evidence from animal studies suggest that chronic elevation of circulating intestinal-generated lipopolysaccharide (LPS) (i.e., metabolic endotoxemia) could play a role in the pathogenesis of insulin resistance. However, the effect of LPS in human muscle is unclear. Moreover, it is unknown whether blockade/down regulation of toll-like receptor (TLR)4 can prevent the effect of LPS on insulin action and glucose metabolism in human muscle cells. In the present study we compared plasma LPS concentrati… Show more

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Cited by 152 publications
(133 citation statements)
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“…In addition, it has been shown that exercise decreases the expression of Toll-like receptor (TLR)2 and TLR4 in immune cells and skeletal muscle [73][74][75], while even short-term bed-rest increases the expression of TLR4 [66]. Importantly, activation of TLRs in skeletal muscle by factors such as lipopolysaccharide (LPS), heat shock protein 60 or NEFA has been suggested to be involved in the development of insulin resistance [73,76]. Moreover, because of exercise-induced increases in adrenaline (epinephrine), cortisol and other factors with immunomodulatory effects, physical activity may also have beneficial effects on immune system function [75].…”
Section: Myokines and Metabolic Regulationmentioning
confidence: 99%
“…In addition, it has been shown that exercise decreases the expression of Toll-like receptor (TLR)2 and TLR4 in immune cells and skeletal muscle [73][74][75], while even short-term bed-rest increases the expression of TLR4 [66]. Importantly, activation of TLRs in skeletal muscle by factors such as lipopolysaccharide (LPS), heat shock protein 60 or NEFA has been suggested to be involved in the development of insulin resistance [73,76]. Moreover, because of exercise-induced increases in adrenaline (epinephrine), cortisol and other factors with immunomodulatory effects, physical activity may also have beneficial effects on immune system function [75].…”
Section: Myokines and Metabolic Regulationmentioning
confidence: 99%
“…Pyruvate oxidation was used to assess the activity of pyruvate dehydrogenase (PDH), the enzyme that catalyzes the oxidation of pyruvate and the provision of glucose-derived acetyl CoA to the TCA. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]-pyruvate oxidation was assessed in a similar manner to fatty acid oxidation with the exception that pyruvate was substituted for BSA-bound palmitic acid. All samples were run in triplicate and data were normalized to total protein content and expressed in nmol/mg protein/h.…”
Section: Serum Endotoxin Was Measured With a Pyrogenementioning
confidence: 99%
“…Once in the circulation, endotoxin binds to the toll-like receptor 4 (TLR4) and activates several proinflammatory pathways (3). This modest elevation in circulating endotoxin, termed "metabolic endotoxemia" (2), has been implicated as a cause for the low-grade systemic inflammation observed in obesity and related metabolic diseases (2,4). Elevated circulating endotoxin has been shown to initiate obesity and insulin resistance in rodent models (4).…”
Section: Introductionmentioning
confidence: 99%
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“…Our data suggest that becoming sedentary leads to greater MT and endotoxemia, which in rodent models initiates reduced Inflammatory processes did not significantly influence the relationship between physical function and insulin sensitivity; however, microbial translocation covariates reduced the association to non-significance insulin signaling effectiveness and metabolic disease (Cani et al, 2007;Amar et al, 2011). This effect of endotoxin and insulin signaling has been replicated in human skeletal muscle myocytes and was reversible with blockade of LPS binding (Liang et al, 2013). Both being sedentary and insulin resistant contribute to reduced muscle anabolic signaling and permit loss of muscle mass, which sets the stage for development of frailty and its clinical consequences.…”
Section: Discussionmentioning
confidence: 61%