Plasma amino acid and metabolite changes in pigs during endotoxemia

Abstract

The nutritional status, especially circulating amino acid (AA) levels, can drastically change during a non-infectious (i.e., LPS) or infectious (e.g., Salmonella) challenge. Thus, study 1 examined the effect of LPS treatment (N = 9, 26.9 ± 1.07 kg BW) on plasma AA and metabolite levels in pigs. Data were used to generate prediction equations establishing mathematical relationships between plasma AA levels and numerous blood metabolites (e.g., total lipid, LDL, HDL, blood urea nitrogen, etc). These equations have the potential to improve the nutritional treatment and recovery of acute and chronically ill patients. Study 2 (19.1 ± 0.37 kg) was a continuation of study 1 except the sampling time was increased from 12 to 24 h. One-half of the pigs in study 2 were treated with LPS (N=15) and the other one-half were saline treated control animals (N = 16). This design allows for monitoring changes in plasma AA and their catabolism in response to endotoxemia. Area under the curve (AUC) was calculated for a selected AA to report AA balances. During the induction phase of an acute challenge (t = -2 to 12 h), analyzed AA were in a negative balance indicating heavy AA catabolism. However, during the recovery phase (t = 12 to 24 h) half of the AA were in a positive balance while the other half were still negative. The ability of equations to accurately predict AA concentrations was tested. Results indicate poor performance possibly due to heavy term biases. Thus, it was concluded that equations need to be revisited and non-linear terms need to be evaluated. Nonetheless, routine clinical blood metabolites can be used to estimate plasma AA levels during immune activation. We successfully established a porcine Salmonella enterica serovar Typhimurium model. Pigs infected with Salmonella had a febrile response for 4 d and exhibited marked changes in their fecal bacterial populations Finally, we investigated plasma changes in N-τ-methyl histidine (NτMH) in healthy and LPS-treated pigs. NτMH— is a post-translationally modified AA that has historically been used as an indirect marker of muscle protein breakdown in rodents and humans. However, the major form (i.e., free or acetylated) of NτMH in pig plasma was unknown. Results indicate that only 15% of plasma NτMH is in the free form and the remainder is acetylated. Furthermore, LPS treated pigs had increased acetylated and total NτMH fractions while free NτMH did not change. Therefore, to accurately monitor plasma changes in NτMH as an indicator of muscle proteolysis, plasma samples must be subjected to acid hydrolysis.