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.
Highlights
In a study in the previous issue of Critical Care, Huang and colleagues [1] observed that, in the critically ill, Adipocyte fatty acid-binding protein (A-FABP or FABP4), known as aP2, is a carrier protein for fatty acids and is expressed primarily in adipocytes and macrophages
Mice deficient in adipose-fatty acid-binding protein (A-FABP) are protected from development of hyperinsulinemia, hyperglycemia, and insulin resistance [3]
Adipocytes obtained from A-FABP-null mice had markedly reduced efficiency of lipolysis in vivo and in vitro [4] and showed a two- to three-fold decrease in fatty acid release, suggesting that A-FABP regulates efflux of fatty acids under normal physiological conditions
Summary
In a study in the previous issue of Critical Care, Huang and colleagues [1] observed that, in the critically ill, Adipocyte fatty acid-binding protein (A-FABP or FABP4), known as aP2 (adipocyte protein 2), is a carrier protein for fatty acids and is expressed primarily in adipocytes and macrophages. Adipocytes obtained from A-FABP-null mice had markedly reduced efficiency of lipolysis in vivo and in vitro [4] and showed a two- to three-fold decrease in fatty acid release, suggesting that A-FABP regulates efflux of fatty acids under normal physiological conditions. Acute insulin secretory response to β-adrenergic stimulation was profoundly suppressed in A-FABP−/− mice compared with their wild-type littermates [4], indicating that A-FABP could regulate systemic insulin sensitivity through its actions on other distal target tissues.
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