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Liver mitochondrial properties from the obesity-resistant Lou/C rat

International Journal of Obesity volume 32, pages 629–638 (2008)Cite this article

Abstract

Objective:

The first objective was to evaluate the influence of caloric intake on liver mitochondrial properties. The second objective was aimed at determining the impact of increasing fat intake on these properties.

Design:

Lou/C rats, displaying an inborn low caloric intake and resistant to diet-induced obesity, were compared to Wistar rats fed either ad libitum or pair-fed. An additional group of Lou/C rats were allowed to increase their fat intake by adjusting their diet from a standard high carbohydrate low-fat diet to a high-fat carbohydrate-free diet.

Measurements:

Hydrogen peroxide (H2O2) generation, oxygen consumption rate ( J O 2 ) , membrane potential (ΔΨ), activity of respiratory chain complexes, cytochrome contents, oxidative phosphorylation efficiency (OPE) and uncoupling protein 2 (UCP2) expression were determined in liver mitochondria.

Results:

H2O2 production was higher in Lou/C than Wistar rats with glutamate/malate and/or succinate, octanoyl-carnitine, as substrates. These mitochondrial features cannot be mimicked by pair-feeding Wistar rats and remained unaltered by increasing fat intake. Enhanced H2O2 production by mitochondria from Lou/C rats is due to an increased reverse electron flow through the respiratory-chain complex I and a higher medium-chain acyl-CoA dehydrogenase activity. While J O 2 was similar over a large range of ΔΨ in both strains, Lou/C rats were able to sustain higher membrane potential and respiratory rate. In addition, mitochondria from Lou/C rats displayed a decrease in OPE that cannot be explained by increased expression of UCP2 but rather to a slip in proton pumping by cytochrome oxidase.

Conclusions:

Liver mitochondria from Lou/C rats display higher reactive oxygen species (ROS) generation but to deplete upstream electron-rich intermediates responsible for ROS generation, these animals increased intrinsic uncoupling of cytochrome oxidase. It is likely that liver mitochondrial properties allowed this strain of rat to display higher insulin sensitivity and resist diet-induced obesity.

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Acknowledgements

This study was supported by a grant from INSERM/INRA (AIP 02 P00275). We thank F Bouillaud (BIOTRAM UPR9078, CNRS, Paris, France) for the kind gift of UCP2 antibody, Cindy Tellier for taking care of the rats and Blandine Garait for practical assistance.

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Authors and Affiliations

  1. Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U884, Université Joseph Fourier, Grenoble Cedex, France

    G Lacraz, K Couturier, N Taleux, B Guigas, H Dubouchaud, X Leverve & R Favier

  2. Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire, CNRS UMR 5123, Université Claude Bernard Lyon, Villeurbanne Cedex, France

    S Servais, B Sibille & D Letexier

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  1. G Lacraz
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Correspondence to R Favier.

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Lacraz, G., Couturier, K., Taleux, N. et al. Liver mitochondrial properties from the obesity-resistant Lou/C rat. Int J Obes 32, 629–638 (2008). https://doi.org/10.1038/sj.ijo.0803779

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