LEUCINE METABOLISM IN TNF-ALPHA-TREATED AND ENDOTOXIN-TREATED RATS - CONTRIBUTION OF HEPATIC TISSUE

The effects of tumor necrosis factor-alpha (TNF-alpha; cachectin) and lipopolysaccharide of Salmonella enteritidis (LPS; endotoxin) on leuci ne metabolism in rats were evaluated in the whole body using intraveno us infusion of L-[1-C-14]leucine and in isolated perfused liver (IPL) using the single-pass perfusion technique with alpha-keto[1-C-14]isoca proate as a tracer for measurement of ketoisocaproic acid (KIC) oxidat ion, and the recirculation technique for measurement of hepatic amino acid exchanges. The data obtained in TNF-alpha and LPS groups were com pared with those obtained in controls. Both TNF-alpha and LPS treatmen t induced an increase of whole body leucine turnover, oxidation, and c learance, As the result of a higher increase of leucine oxidation than of incorporation into the pool of body proteins, the fractional oxida tion of leucine was increased. The fractional rate of protein synthesi s increased significantly in the spleen (both in TNF-alpha and LPS rat s), in blood plasma, liver, colon, kidneys, gastrocnemius muscle (in L PS rats), and in lungs (TNF-alpha-treated rats), whereas it decreased in the jejunum (LPS rats). In IPL of TNF-alpha- and LPS-treated rats a decrease of KIC oxidation and higher uptake of branched-chain amino a cids (BCAA; valine, leucine, and isoleucine) were observed when compar ed with control animals. We hypothesize that the negative consequences of increased whole body proteolysis and of increased oxidation of BCA A induced by TNF-alpha and/or LPS are reduced by decreased activity of hepatic branched-chain ketoacid dehydrogenase that can help resupply BCAA to the body.