Lipopolysaccharide (LPS) increases the in vivo oxidation of branched-chain amino acids in the rat: a cytokine-mediated effect.

Septic rats (as induced by cecal puncture and ligation) showed an increased rate of in vivo leucine oxidation as measured from the formation of 14CO2 from an intravenously injected [1-14C]leucine tracer dose. Acute lipopolysaccharide (LPS) administration (1 mg/kg) to rats caused a similar effect on the rate of in vivo leucine oxidation. Additionally, both tumour necrosis factor-alpha (TNF) and interleukin-1-alpha (IL-1), in an acute dose of 100 micrograms/kg, also increased the rate of the oxidation of the amino acid, although only IL-1 caused a similar increase to that observed following LPS. The observed increased leucine oxidation was related to lower leucine concentrations both in LPS- and cytokine-treated rats. Important decreases were also observed in the other branched-chain amino acids (valine and isoleucine) in the LPS- and IL-1-treated animals. Isolated incubated muscles from TNF- and IL-1-treated rats did not show any changes in the rate of leucine utilization, thus suggesting that the mechanism by which the cytokines stimulate whole-body leucine oxidation is not based on an increase in the activity of the enzymatic machinery responsible for leucine oxidation. Additionally, glucocorticoids do not seem to mediate the enhanced in vivo oxidation of the amino acid since, although they are increased by both LPS and cytokines, treatment of the animals with RU486 (a glucocorticoid antagonist) was not able to suppress the effects of the cytokine on in vivo leucine oxidation.