The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

Abstract

SummaryWe examined the effects of lipopolysaccharide (LPS) injection on body temperature and plasma free amino acid concentrations in rats. A catheter was placed in the jugular vein of the rats in order to draw blood from and to inject LPS into awake animals. On the day of the experiment, body temperature was recorded during the experiment (330 min) and blood was drawn before and at several time points after injection of LPS (10 g/kg body weight). Body temperature in LPS-treated rats began to rise ~30 min after injection with a peak at 120 min, and afterward remained ~1˚C higher than that in control rats through the end of the experiment. Concentrations of many plasma free amino acids were decreased by LPS treatment, with a nadir at ~120 min, and then were increased to the level of or over the control. It appears that thermoregulatory responses induced by LPS treatment may be related to alterations in plasma free amino acid concentrations. Effects of LPS treatment on the dynamics of plasma free branched-chain amino acid (BCAA) concentrations in rats with peroral or intravenous administration of BCAAs were also examined. The results showed that the rise in plasma BCAA concentrations after peroral BCAA administration was significantly suppressed by LPS treatment, but the dynamics of plasma BCAAs after intravenous administration was not affected by LPS, suggesting that LPS treatment inhibited the intestinal absorption of BCAAs into the circulation. These results suggest that the availability of administered BCAAs to the body tissues during sepsis is higher following parenteral than peroral administration. Key Words endotoxin, lipopolysaccharide, plasma amino acids, branched-chain amino acids (BCAA), body temperature Sepsis induces several metabolic responses including negative nitrogen balance and loss of lean body mass. This catabolic phase is associated with muscle protein breakdown ( 1 , 2 ) and increased whole body amino acid metabolism ( 3 ). Glutamine metabolism and branchedchain amino acid (BCAA) catabolism are especially prominent; glutamine production is increased through proteolysis and BCAAs are actively oxidized in skeletal muscles during sepsis ( 4 , 5 ). Therefore, administration of these amino acids is considered to have a potential to alleviate the septic conditions ( 6 , 7 ).Administration of bacterial lipopolysaccharide (LPS) preparations to laboratory animals is widely used to reproduce the septic state, in which various metabolic as well as thermoregulatory responses are induced in association with systemic inflammation. It has been reported that the thermoregulatory response to LPS administration is dependent upon the dose of LPS and ambient temperature ( 8 ). In many studies ( 5 , 9 -12 ), high, shock-inducing doses such as 500 g LPS/kg body weight (BW) or more have been used and these doses caused pronounced hypothermia ( 8 ). On the other hand, it has been reported that intravenous administration of low or intermediary doses (less than 10 g/kg BW) of LPS elicits fever when animals are kept i...

Post-ruminal branched-chain amino acid supplementation and intravenous lipopolysaccharide infusion alter blood metabolites, rumen fermentation, and nitrogen balance of beef steers1

“…Plasma Asn concentrations decreased in LPSchallenged steers, which is a consistent response among studies with cattle (Waggoner et al, 2009a,b;Carter et al, 2010) and other species (Asai et al, 2008). Both Asn and Gln are activators of ornithine decarboxylase for polyamine synthesis in proliferating cells (Ray and Johnson, 2014), and Asn reduces intestinal damage of pigs after LPS exposure (Chen et al, 2016).…”

Amino acids inhibit kynurenic acid formation via suppression of kynurenine uptake or kynurenic acid synthesis in rat brain in vitro

“…In the present study, the amino acids that inhibited KYN uptake are consistent with substrate amino acids of LAT 1 rather than LAT 2, suggesting a critical role of LAT 1 in KYN uptake in the brain. K m values of LAT 1 for leucine, isoleucine, methionine, phenylalanine, and tyrosine are 15–30 μmol/L, around physiological concentrations (Asai et al 2008 ), indicating higher affinity than for KYN (Yanagida et al 2001 ). The other amino acids (glutamine and aspartate) have low affinity for LAT 1 ( K m = 1.5–2 mmol/L), and are not substrates of LAT nor affect tissue KYN concentration.…”

“…We precisely investigated the effect of 10 amino acids on KYNA production and KYN uptake at 3 μmol/L–3 mmol/L. The physiological concentrations of leucine, isoleucine, phenylalanine, methionine, tyrosine, alanine, aspartate, cysteine, glutamine, and glutamate are approximately 150, 90, 60, 50, 70, 400, 10, 10, 700, and 80 μmol/L in rat plasma, respectively (Asai et al 2008 ). Interestingly, all 10 amino acids partially inhibited KYNA production at physiological concentrations, with IC 50 values of most amino acids for KYNA production or KYN uptake around physiological levels.…”

“…LATs are known to transport both branched chain amino acids (e.g., valine, leucine and isoleucine) and aromatic amino acids (e.g., tyrosine, phenylalanine, and tryptophan). Several findings show that LATs transport amino acids with higher affinity than KYN in tumor cell lines (Fukui et al 1991 ; Speciale et al 1989 ; Asai et al 2008 ; Yanagida et al 2001 ), and changes in physiological concentrations of these amino acids may affect KYN transport into the brain.…”

Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride‐induced acute phase response

“…This study is the first to demonstrate that, 3 h after an LPS injection, there is an increased relative isotopic abundance in plasma amino acids (alanine, proline and threonine) relative to their levels prior to LPS injection and relative to the levels of saline‐injected controls. Asai et al demonstrated that plasma concentrations of individual amino acids quickly decrease then increase in the first 6 h of the response to endotoxin with a pivotal point at 3 h after injection in rats 29. Phenotypic variation due to the LPS stimulus and the timing of the 3‐h sample, a potential inflection point in plasma amino acid concentration, may have led to a high degree of variability in the observed shift in amino acid isotope abundance.…”