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Abstract

Hepatic Encephalopathy (HE) in both chronic and acute liver failure is associated with hyperammonemia and energetic changes in brain and peripheral organs. In animal models and in patients with mild HE, L-carnitine has been shown to be protective. In order to investigate the effect of L-carnitine on energy- and fatty acid metabolism, 1H- and 13C-NMR spectroscopy was used to measure metabolic pathways in brain and muscle following administration of [U-13C]glucose to rats with mild HE and in rats with ammonia-precipitated encephalopathy. Portacaval anastomosis in the rat resulted in a broad spectrum of neurobehavioral changes, such as a 80 impaired locomotor activity, which was largely prevented by L-carnitine. Concomitantly, L-carnitine improved mitochondrial energy metabolism and fatty acid catabolism in brain and muscle. In ammonia-precipitated encephalopathy, L-carnitine considerably delayed the time to coma of the rats, concomitantly to a prevention of ammonia-induced increased lactate synthesis in the brain. These results demonstrate that L-carnitine acts both in the brain and in the muscle by improvement of mitochondrial metabolism and fatty acid catabolism, which might explain L-carnitine’s therapeutic benefit in the prevention of mild HE and ammonia-precipitated encephalopathy in cirrhotic patients.