Volume 145,number 2 FEBSLETTERS August 1982 Inhibitory effect of D-galactosamine administration on fatty acid oxidation in rat hepatocytes Marise Mangeney-Andreani, Olivier Sire, Jacqueline Montagne-Clavel, Roger Nordmann and Joseph Nordmann zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO Laboratoire de Biochimie de la FacultP de MPdecine de Paris-Ouest et Groupe de Recherches (U 72) de I’INSERM, 45, rue des Saints-P&es, 75006 Paris, France Received 10 July 1982 D-Galactosamine Fatty liver Fatty acid oxidation Palmitoyl L- carnitine 1. INTRODUCTION Important similarities between D-galactos- amine (GaIN)-mediated hepatocellular necrosis Hepatocytes M itochondria and viral hepatitis have been emphasized [l]. The necrosis induced by GaIN is however accom- panied by hepatic triacylglycerol (TAG) accumu- lation [2], an association not present in human viral hepatitis. as 3 h after a single dose of GaIN. Having con- firmed that no increase in the serum FFA level is apparent at this stage of intoxication, this pre- liminary report was devoted to the study of the rate of fatty acid oxidation in isolated hepatocytes and mitochondria from GaIN treated rats. Koff et al. [3] first reported data suggesting that impaired hepatic lipoprotein release, presumably due to inhibition of synthesis of the protein moiety of very low density lipoproteins, is the mechanism of the GaIN-induced fatty liver. In further studies, in which a lower GaIN dose was used, Sabesin and Koff [4], observed, in the absence of any necrosis, the development of steatosis which was considered by the authors to result from an increased free fat- ty acid (FFA) influx rather than to an inhibition of TAG release. This hypothesis was further sup- ported by Katterman and Sirowej (51 who reported that the plasma FFA level was increased 24 and 48 h after the intraperitoneal injection of GaIN. However, as no increase in plasma FFA was ob- served by these authors 12 h after GaIN admin- istration, and since TAG accumulation had al- ready occurred 4 h after GaIN administration, it seems highly unlikely that an increased FFA influx may play a major role in the development of the GaIN-induced fatty liver. The results show (i) that palmitate but not oc- tanoate oxidation was markedly depressed in hepatocytes from GaIN treated rats, and (ii) that palmitoyl CoA but not palmitoyl L-carnitine ox- idation in isolated mitochondria was affected. These data indicate therefore that GaIN admin- istration impairs the rate of fatty acid oxidation in the liver, and suggest that this action results from a disturbance located at the carnitine palmitoyl- transferase I level. 2. MATERIALS AND METHODS Collagenase from Clostridium histolyticum (Type IV), D( +) galactosamine-HCl, palmitoyl L-camitine-HCl, L-camitine and bovine serum al- bumin (fatty acid free-fraction V) were purchased from Sigma Chemical Co., [ I-t4C]octanoic acid sodium salt (spec. act. 30 mCi/mmol) and [U-mC]- palmitic acid (spec. act. 403 mCi/mmol) from Amersham. All other reagents were of analytical grade or of the highest purity available (Sigma, Merck or Fluka). The purpose of the present study was to estab- lish the factor(s) responsible for the TAG ac- cumulation which is observed in rat liver as early Male Wistar rats (C.E.R.J., F-53680) weighing 200-240 g were kept at 20-22°C with a photo- period of 12D-12N. They were starved overnight before the experiments and given water ad libitum. Published by Elsevier Biomedical Press CO145793/82/OOOC-COOOooo/$2.75 0 1982 Federation of European Biochemical Societies 267