Leucine metabolism in TNF-α- and endotoxin-treated rats: contribution of hepatic tissue

Abstract

The effects of tumor necrosis factor-α (TNF-α; cachectin) and lipopolysaccharide of Salmonella enteritidis (LPS; endotoxin) on leucine metabolism in rats were evaluated in the whole body using intravenous infusion ofl-[1-14C]leucine and in isolated perfused liver (IPL) using the single-pass perfusion technique with α-keto[1-14C]isocaproate as a tracer for measurement of ketoisocaproic acid (KIC) oxidation, and the recirculation technique for measurement of hepatic amino acid exchanges. The data obtained in TNF-α and LPS groups were compared with those obtained in controls. Both TNF-α and LPS treatment induced an increase of whole body leucine turnover, oxidation, and clearance. As the result of a higher increase of leucine oxidation than of incorporation into the pool of body proteins, the fractional oxidation of leucine was increased. The fractional rate of protein synthesis increased significantly in the spleen (both in TNF-α and LPS rats), in blood plasma, liver, colon, kidneys, gastrocnemius muscle (in LPS rats), and in lungs (TNF-α-treated rats), whereas it decreased in the jejunum (LPS rats). In IPL of TNF-α- and LPS-treated rats a decrease of KIC oxidation and higher uptake of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) were observed when compared with control animals. We hypothesize that the negative consequences of increased whole body proteolysis and of increased oxidation of BCAA induced by TNF-α and/or LPS are reduced by decreased activity of hepatic branched-chain ketoacid dehydrogenase that can help resupply BCAA to the body.

Inflammation Nutritional State and Outcome in End Stage Renal Disease

“…On the one hand increased cytokine levels The initial name for TNF was cachectin, reflecting this effect on body composition [32]. The effect of cyto-would alter both plasma composition and body morphometry consistent with what is observed during pure kines and protein calorie malnutrition on negative acute phase proteins levels in serum are also essentially the uncomplicated calorie malnutrition.…”

Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle

“…Amino acids are mobilized from skeletal muscle and reused by other tissues, such as the liver, for the synthesis of acute-phase proteins (21). Although the response to infection is often viewed as a systemic event, local synthesis of proinflammatory cytokines in skeletal muscle may also promote muscle wasting.…”

Profiling of dynamic changes in hypermetabolic livers

“…In order to characterize the metabolic state of the liver in the absence of systemic effects, most studies have used isolated perfused liver systems to measure hepatic oxygen consumption in septic rats (Dahn et al, 1996), leucine metabolism in endotoxin-treated rats (Holecek et al, 1997), and acute-phase protein synthesis in burned rats (Hiyama et al, 1991). These studies were limited by the small number of parameters measured and neglected information contained in the correlations among metabolites that would result from a comprehensive analysis.…”