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Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets

Published online by Cambridge University Press:  19 August 2011

J. Keller ,
R. Ringseis ,
A. Koc ,
I. Lukas ,
H. Kluge  and
K. Eder
J. Keller
Affiliation:
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany
R. Ringseis
Affiliation:
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany
A. Koc
Affiliation:
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany
I. Lukas
Affiliation:
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany
H. Kluge
Affiliation:
Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Von-Danckelmann-Platz 2, 06120 Halle (Saale), Germany
K. Eder*
Affiliation:
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany
*
†E-mail: klaus.eder@ernaehrung.uni-giessen.de
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Abstract

Supplementation of carnitine has been shown to improve performance characteristics such as protein accretion in growing pigs. The molecular mechanisms underlying this phenomenon are largely unknown. Based on recent results from DNA microchip analysis, we hypothesized that carnitine supplementation leads to a downregulation of genes of the ubiquitin proteasome system (UPS). The UPS is the most important system for protein breakdown in tissues, which in turn could be an explanation for increased protein accretion. To test this hypothesis, we fed sixteen male, four-week-old piglets either a control diet or the same diet supplemented with carnitine and determined the expression of several genes involved in the UPS in the liver and skeletal muscle. To further determine whether the effects of carnitine on the expression of genes of the UPS are mediated directly or indirectly, we also investigated the effect of carnitine on the expression of genes of the UPS in cultured C2C12 myotubes and HepG2 liver cells. In the liver of piglets fed the carnitine-supplemented diet, the relative mRNA levels of atrogin-1, E214k and Psma1 were lower than in those of the control piglets (P < 0.05). In skeletal muscle, the relative mRNA levels of atrogin-1, MuRF1, E214k, Psma1 and ubiquitin were lower in piglets fed the carnitine-supplemented diet than that in control piglets (P < 0.05). Incubating C2C12 myotubes and HepG2 liver cells with increasing concentrations of carnitine had no effect on basal and/or hydrocortisone-stimulated mRNA levels of genes of the UPS. In conclusion, this study shows that dietary carnitine decreases the transcript levels of several genes involved in the UPS in skeletal muscle and liver of piglets, whereas carnitine has no effect on the transcript levels of these genes in cultivated HepG2 liver cells and C2C12 myotubes. These data suggest that the inhibitory effect of carnitine on the expression of genes of the UPS is mediated indirectly, probably via modulating the release of inhibitors of the UPS such as IGF-1. The inhibitory effect of carnitine on the expression of genes of the UPS might explain, at least partially, the increased protein accretion in piglets supplemented with carnitine.

Keywords

carnitineubiquitin proteasome systemskeletal muscleliverpig
Type
Full Paper
Information
animal , Volume 6 , Issue 1 , January 2012 , pp. 70 - 78
Copyright
Copyright © The Animal Consortium 2011

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