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Serum adipocyte fatty acid-binding protein in the critically ill.

Das UN - Crit Care (2013)

Bottom Line: Increased production of pro-inflammatory cytokines, free radicals, and eicosanoids has been detected in sepsis and other critical illnesses but could also be due to decreased synthesis and release of anti-inflammatory molecules.Increased serum adipose-fatty acid-binding protein (A-FABP) levels can cause insulin resistance and have been reported in the critically ill, serve as a marker of prognosis, and thus link metabolic homeostasis and inflammation.Serial measurement of these pro- and anti-inflammatory molecules and correlation of their levels to the progression to or recovery from (or both) sepsis and other inflammatory processes may form a new approach to predict prognosis in inflammatory conditions and eventually could lead to the development of new therapeutic strategies.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Sepsis due to unabated inflammation is common. Increased production of pro-inflammatory cytokines, free radicals, and eicosanoids has been detected in sepsis and other critical illnesses but could also be due to decreased synthesis and release of anti-inflammatory molecules. Increased serum adipose-fatty acid-binding protein (A-FABP) levels can cause insulin resistance and have been reported in the critically ill, serve as a marker of prognosis, and thus link metabolic homeostasis and inflammation. A-FABP can be linked to the expression of Toll-like receptors, macrophage activation, synthesis and release of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, activation of cyclooxygenase 2 (COX-2) expression, and eicosanoid synthesis, events that can cause insulin resistance and initiation and progression of inflammation and sepsis. Unsaturated fatty acids and their anti-inflammatory products, such as lipoxins, resolvins, and protectins, may suppress A-FABP expression, inhibit macrophage and COX-2 activation, and decrease production of pro-inflammatory cytokines and ultimately could lead to a decrease in insulin resistance and resolution of inflammation and recovery from sepsis. Serial measurement of these pro- and anti-inflammatory molecules and correlation of their levels to the progression to or recovery from (or both) sepsis and other inflammatory processes may form a new approach to predict prognosis in inflammatory conditions and eventually could lead to the development of new therapeutic strategies.

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Interaction(s) among adipose-fatty acid-binding protein (A-FABP), Toll-like receptor (TLR), cytokines, free radicals, unsaturated fatty acids, and their products and inflammation and resolution of inflammation. Infections, injuries (including surgery), and high-fat diet activate macrophages and TLRs, leading to secretion of increased amounts of pro-inflammatory cytokines that, in turn, produce an excess of free radicals. Pro-inflammatory cytokines, TLRs, and free radicals activate A-FABP and cyclooxygenase 2 (COX-2), leading to increased production of pro-inflammatory prostaglandins (PGs), leukotrienes (LTs), and thromboxanes (TXs) from unsaturated fatty acids and decreases in the synthesis and release of anti-inflammatory lipoxins (LXs), resolvins (RSVs), and protectins (PRTs). Blocking the expression of A-FABP and TLRs will suppress inflammation. Unsaturated fatty acids and LXs, RSVs, and PRTs are expected to suppress macrophage activation and expression of A-FABP and TLRs and inhibit inflammation. Increased expression of A-FABP also occurs in obesity, type 2 diabetes mellitus (DM), and coronary heart disease (CHD). Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage activation, increased expression of A-FABP, and increased production of PGs, LTs, TXs, and free radicals enhance insulin resistance in infections and sepsis. AA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HMGB1, high-mobility group box 1; LPS, lipopolysaccharide; NL, nitrolipid; NO, nitric oxide; ROS, reactive oxygen species.
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Figure 1: Interaction(s) among adipose-fatty acid-binding protein (A-FABP), Toll-like receptor (TLR), cytokines, free radicals, unsaturated fatty acids, and their products and inflammation and resolution of inflammation. Infections, injuries (including surgery), and high-fat diet activate macrophages and TLRs, leading to secretion of increased amounts of pro-inflammatory cytokines that, in turn, produce an excess of free radicals. Pro-inflammatory cytokines, TLRs, and free radicals activate A-FABP and cyclooxygenase 2 (COX-2), leading to increased production of pro-inflammatory prostaglandins (PGs), leukotrienes (LTs), and thromboxanes (TXs) from unsaturated fatty acids and decreases in the synthesis and release of anti-inflammatory lipoxins (LXs), resolvins (RSVs), and protectins (PRTs). Blocking the expression of A-FABP and TLRs will suppress inflammation. Unsaturated fatty acids and LXs, RSVs, and PRTs are expected to suppress macrophage activation and expression of A-FABP and TLRs and inhibit inflammation. Increased expression of A-FABP also occurs in obesity, type 2 diabetes mellitus (DM), and coronary heart disease (CHD). Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage activation, increased expression of A-FABP, and increased production of PGs, LTs, TXs, and free radicals enhance insulin resistance in infections and sepsis. AA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HMGB1, high-mobility group box 1; LPS, lipopolysaccharide; NL, nitrolipid; NO, nitric oxide; ROS, reactive oxygen species.

Mentions: Under normal physiological conditions, a balance between pro- and anti-inflammatory molecules is maintained. A tilting of this balance in favor of the former would lead to initiation and progression of inflammation, insulin resistance, and consequent tissue damage [17]. Such an inflammatory process could be due not only to increased expression of A-FABP and augmented production of pro-inflammatory molecules but also to deficiency of anti-inflammatory molecules such as IL-4, IL-10, lipoxins, resolvins, and protectins (Figure 1). In this context, it is noteworthy that A-FABP suppresses cardiomyocyte contraction [18] whereas unsaturated fatty acids seem to prevent cardiac failure [19], reinforcing close interaction(s) among various pro- and anti-inflammatory molecules and their role in sepsis. Hence, a better understanding of the interaction(s) among these molecules in inflammatory conditions is essential in order to develop meaningful and novel therapeutic strategies especially for sepsis.


Serum adipocyte fatty acid-binding protein in the critically ill.

Das UN - Crit Care (2013)

Interaction(s) among adipose-fatty acid-binding protein (A-FABP), Toll-like receptor (TLR), cytokines, free radicals, unsaturated fatty acids, and their products and inflammation and resolution of inflammation. Infections, injuries (including surgery), and high-fat diet activate macrophages and TLRs, leading to secretion of increased amounts of pro-inflammatory cytokines that, in turn, produce an excess of free radicals. Pro-inflammatory cytokines, TLRs, and free radicals activate A-FABP and cyclooxygenase 2 (COX-2), leading to increased production of pro-inflammatory prostaglandins (PGs), leukotrienes (LTs), and thromboxanes (TXs) from unsaturated fatty acids and decreases in the synthesis and release of anti-inflammatory lipoxins (LXs), resolvins (RSVs), and protectins (PRTs). Blocking the expression of A-FABP and TLRs will suppress inflammation. Unsaturated fatty acids and LXs, RSVs, and PRTs are expected to suppress macrophage activation and expression of A-FABP and TLRs and inhibit inflammation. Increased expression of A-FABP also occurs in obesity, type 2 diabetes mellitus (DM), and coronary heart disease (CHD). Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage activation, increased expression of A-FABP, and increased production of PGs, LTs, TXs, and free radicals enhance insulin resistance in infections and sepsis. AA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HMGB1, high-mobility group box 1; LPS, lipopolysaccharide; NL, nitrolipid; NO, nitric oxide; ROS, reactive oxygen species.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3672535&req=5

Figure 1: Interaction(s) among adipose-fatty acid-binding protein (A-FABP), Toll-like receptor (TLR), cytokines, free radicals, unsaturated fatty acids, and their products and inflammation and resolution of inflammation. Infections, injuries (including surgery), and high-fat diet activate macrophages and TLRs, leading to secretion of increased amounts of pro-inflammatory cytokines that, in turn, produce an excess of free radicals. Pro-inflammatory cytokines, TLRs, and free radicals activate A-FABP and cyclooxygenase 2 (COX-2), leading to increased production of pro-inflammatory prostaglandins (PGs), leukotrienes (LTs), and thromboxanes (TXs) from unsaturated fatty acids and decreases in the synthesis and release of anti-inflammatory lipoxins (LXs), resolvins (RSVs), and protectins (PRTs). Blocking the expression of A-FABP and TLRs will suppress inflammation. Unsaturated fatty acids and LXs, RSVs, and PRTs are expected to suppress macrophage activation and expression of A-FABP and TLRs and inhibit inflammation. Increased expression of A-FABP also occurs in obesity, type 2 diabetes mellitus (DM), and coronary heart disease (CHD). Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage activation, increased expression of A-FABP, and increased production of PGs, LTs, TXs, and free radicals enhance insulin resistance in infections and sepsis. AA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HMGB1, high-mobility group box 1; LPS, lipopolysaccharide; NL, nitrolipid; NO, nitric oxide; ROS, reactive oxygen species.
Mentions: Under normal physiological conditions, a balance between pro- and anti-inflammatory molecules is maintained. A tilting of this balance in favor of the former would lead to initiation and progression of inflammation, insulin resistance, and consequent tissue damage [17]. Such an inflammatory process could be due not only to increased expression of A-FABP and augmented production of pro-inflammatory molecules but also to deficiency of anti-inflammatory molecules such as IL-4, IL-10, lipoxins, resolvins, and protectins (Figure 1). In this context, it is noteworthy that A-FABP suppresses cardiomyocyte contraction [18] whereas unsaturated fatty acids seem to prevent cardiac failure [19], reinforcing close interaction(s) among various pro- and anti-inflammatory molecules and their role in sepsis. Hence, a better understanding of the interaction(s) among these molecules in inflammatory conditions is essential in order to develop meaningful and novel therapeutic strategies especially for sepsis.

Bottom Line: Increased production of pro-inflammatory cytokines, free radicals, and eicosanoids has been detected in sepsis and other critical illnesses but could also be due to decreased synthesis and release of anti-inflammatory molecules.Increased serum adipose-fatty acid-binding protein (A-FABP) levels can cause insulin resistance and have been reported in the critically ill, serve as a marker of prognosis, and thus link metabolic homeostasis and inflammation.Serial measurement of these pro- and anti-inflammatory molecules and correlation of their levels to the progression to or recovery from (or both) sepsis and other inflammatory processes may form a new approach to predict prognosis in inflammatory conditions and eventually could lead to the development of new therapeutic strategies.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Sepsis due to unabated inflammation is common. Increased production of pro-inflammatory cytokines, free radicals, and eicosanoids has been detected in sepsis and other critical illnesses but could also be due to decreased synthesis and release of anti-inflammatory molecules. Increased serum adipose-fatty acid-binding protein (A-FABP) levels can cause insulin resistance and have been reported in the critically ill, serve as a marker of prognosis, and thus link metabolic homeostasis and inflammation. A-FABP can be linked to the expression of Toll-like receptors, macrophage activation, synthesis and release of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, activation of cyclooxygenase 2 (COX-2) expression, and eicosanoid synthesis, events that can cause insulin resistance and initiation and progression of inflammation and sepsis. Unsaturated fatty acids and their anti-inflammatory products, such as lipoxins, resolvins, and protectins, may suppress A-FABP expression, inhibit macrophage and COX-2 activation, and decrease production of pro-inflammatory cytokines and ultimately could lead to a decrease in insulin resistance and resolution of inflammation and recovery from sepsis. Serial measurement of these pro- and anti-inflammatory molecules and correlation of their levels to the progression to or recovery from (or both) sepsis and other inflammatory processes may form a new approach to predict prognosis in inflammatory conditions and eventually could lead to the development of new therapeutic strategies.

Show MeSH
Related in: MedlinePlus