Effect of short-term intralipid infusion on the immune response during low-dose endotoxemia in humans

Abstract

Novel anti-inflammatory effects of insulin have recently been described, and insulin therapy to maintain euglycemia suppresses the plasma levels of free fatty acids (FFA) and increases the survival of critically ill patients. We aimed to explore the effect of short-term high levels of plasma FFA on the inflammatory response to a low dose of endotoxin. Fourteen healthy male volunteers underwent the following two trials in a randomized crossover design: 1) continuous infusion of 20% Intralipid [0.7 ml·kg−1·h−1(1.54 g/kg)] for 11 h, and 2) infusion of isotonic saline for 11 h (control). In each trial, heparin was given to activate lipoprotein lipase, and an intravenous bolus of endotoxin (0.1 ng/kg) was given after 6 h of Intralipid/saline infusion. Blood samples and muscle and fat biopsies were obtained before the Intralipid/saline infusion and before as well as after infusion of an endotoxin bolus. Plasma levels of FFA, triglycerides, and glycerol were markedly increased during the Intralipid infusion. Endotoxin exposure induced an increase in plasma levels of TNF-α, IL-6, and neutrophils and further stimulated gene expression of TNF-α and IL-6 in both skeletal muscle and adipose tissue. The systemic inflammatory response to endotoxin was significantly pronounced during Intralipid infusion. Short-term hyperlipidemia enhances the inflammatory response to endotoxin, and skeletal muscle and adipose tissue are capable of producing essential inflammatory mediators after endotoxin stimulation.

Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance

“…LPS exposure induced an increase in plasma levels of TNF-a, IL-6 and neutrophil count. 35 NGAL was significantly higher in patients with type 2 diabetes compared with that in subjects with NGT. Interestingly, we have also found an inverse association between circulating NGAL and insulin secretion, which is in line with the higher NGAL concentration in patients with type 2 diabetes.…”

Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans

“…Lipid infusion has also been shown to increase circulating cytokines and in turn induce a proinflammatory status and insulin resistance (33). It has been proposed that saturated FAs can activate the innate immune system and inflammatory pathways via binding to toll-like receptor (TLR)4, which in turn leads to an increase in myocellular ceramide content, which will lead to insulin resistance by direct inhibition of Akt (23).…”

The relationship between circulating neutrophil gelatinase-associated lipocalin and early alteration of metabolic parameters is associated with dietary saturated fat intake in non-diabetic Korean women

“…Erridge et al [38] also identified that fat intake leads to increase of LPS levels in human bloodstream. In addition, intra-lipid infusion significantly pronounced systemic inflammatory response to LPS [39]. In fact, immune system homeostasis can be challenged by continuous external insults, such as SFA-rich diets, pathogen-associated molecular patterns (i.e.…”