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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/E110    most recent 00407.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Romestaing, C. Articles by Sibille, B. Search for Related Content PubMed PubMed Citation Articles by Romestaing, C. Articles by Sibille, B.

Mitochondrial adaptations to steatohepatitis induced by a methionine- and choline-deficient diet

¹Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire, UMR 5123 Centre National de la Recherche Scientifique, Lyon; ²Imagerie Fonctionnelle et Métabolique en Oncologie, Service d'hépatogastroentérologie et de nutrition, Centre Hospitalier Universitaire Caen; ³Laboratoire de Bioénergétique Fondamentale et Appliquée, Institut National de la Santé et de la Recherche Médicale, Grenoble, France; and ⁴Laboratoire Régulation du Métabolisme Energétique Cellulaire, UMR 5095, Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires, Bordeaux, France

Submitted 27 June 2007 ; accepted in final form 5 November 2007

Nonalcoholic fatty liver disease (NAFLD) has become common liver disease in Western countries. There is accumulating evidence that mitochondria play a key role in NAFLD. Nevertheless, the mitochondrial consequences of steatohepatitis are still unknown. The bioenergetic changes induced in a methionine- and choline-deficient diet (MCDD) model of steatohepatitis were studied in rats. Liver mitochondria from MCDD rats exhibited a higher rate of oxidative phosphorylation with various substrates, a rise in cytochrome oxidase (COX) activity, and an increased content in cytochrome aa₃. This higher oxidative activity was associated with a low efficiency of the oxidative phosphorylation (ATP/O, i.e., number of ATP synthesized/natom O consumed). Addition of a low concentration of cyanide, a specific COX inhibitor, restored the efficiency of mitochondria from MCDD rats back to the control level. Furthermore, the relation between respiratory rate and protonmotive force (in the nonphosphorylating state) was shifted to the left in mitochondria from MCDD rats, with or without cyanide. These results indicated that, in MCDD rats, mitochondrial ATP synthesis efficiency was decreased in relation to both proton pump slipping at the COX level and increased proton leak although the relative contribution of each phenomenon could not be discriminated. MCDD mitochondria also showed a low reactive oxygen species production and a high lipid oxidation potential. We conclude that, in MCDD-fed rats, liver mitochondria exhibit an energy wastage that may contribute to limit steatosis and oxidative stress in this model of steatohepatitis.

nonalcoholic steatohepatitis; mitochondria; uncoupling