Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet

• Published in: PloS one 2011-09, Vol.6 (9), p.e24084
• Main Authors: Serviddio, Gaetano, Giudetti, Anna M, Bellanti, Francesco, Priore, Paola, Rollo, Tiziana, Tamborra, Rosanna, Siculella, Luisa, Vendemiale, Gianluigi, Altomare, Emanuele, Gnoni, Gabriele V
• Format: Article
• Language: English
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - metabolism; Acetyl-CoA Carboxylase - metabolism; Animals; Biochemistry; Biology; Blood Glucose - drug effects; Blood Glucose - metabolism; Carbon dioxide; Carnitine; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - metabolism; Cell Membrane Permeability - drug effects; Choline; Choline - administration & dosage; Choline - pharmacology; Cytochrome; Diet; Environmental science; Enzyme Assays; Enzymes; Fatty acids; Fatty Acids - blood; Fatty Acids - metabolism; Feeding Behavior - drug effects; Gene Expression Regulation, Enzymologic - drug effects; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Insulin resistance; Internal medicine; Ketone bodies; Ketones; Laboratories; Lipids; Liver; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver cancer; Liver diseases; Male; Malonyl Coenzyme A - pharmacology; Medicine; Methionine; Methionine - administration & dosage; Methionine - deficiency; Methionine - pharmacology; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - enzymology; Mitochondrial Membranes - drug effects; Mitochondrial Membranes - metabolism; Molecular biology; mRNA; Oxidation; Oxidation-Reduction - drug effects; Oxidation-reduction reactions; Oxidative stress; Palmitic Acid - metabolism; Pathogenesis; Physics; Proteins; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024084

There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2) and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.