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Supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway and down regulates the E3 ligase MuRF1 in skeletal muscle of rats

Keller, Janine ; Couturier, Aline ; Haferkamp, Melanie ; Most, Erika ; Eder, Klaus


Originalveröffentlichung: (2013) Nutrition & Metabolism 10(1):28 doi:10.1186/1743-7075-10-28
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URN: urn:nbn:de:hebis:26-opus-100530
URL: http://geb.uni-giessen.de/geb/volltexte/2013/10053/

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Freie Schlagwörter (Englisch): carnitine , rat , muscle , Ubiquitin-proteasome system , IGF-1/PI3K/Akt signalling pathway
Sammlung: Open Access - Publikationsfonds
Universität Justus-Liebig-Universität Gießen
Fachgebiet: Medizin
DDC-Sachgruppe: Landwirtschaft
Dokumentart: Aufsatz
Sprache: Deutsch
Erstellungsjahr: 2013
Publikationsdatum: 20.08.2013
Kurzfassung auf Englisch: BACKGROUND:Recently, it has been shown that carnitine down-regulates genes involved in the ubiquitin-proteasome system (UPS) in muscle of pigs and rats. The mechanisms underlying this observation are yet unknown. Based on the previous finding that carnitine increases plasma IGF-1 concentration, we investigated the hypothesis that carnitine down-regulates genes of the UPS by modulation of the of the IGF-1/PI3K/Akt signalling pathway which is an important regulator of UPS activity in muscle. METHODS:Male Sprague-Dawley rats, aged four weeks, were fed either a control diet with a low native carnitine concentration or the same diet supplemented with carnitine (1250 mg/kg diet) for four weeks. Components of the UPS and IGF-1/PI3K/Akt signalling pathway in skeletal muscle were examined. RESULTS:Rats fed the diet supplemented with carnitine had lower mRNA and protein levels of MuRF1, the most important E3 ubiquitin ligase in muscle, decreased concentrations of ubiquitin-protein conjugates in skeletal muscle and higher IGF-1 concentration in plasma than control rats (P < 0.05). Moreover, in skeletal muscle of rats fed the diet supplemented with carnitine there was an activation of the PI3K/Akt signalling pathway, as indicated by increased protein levels of phosphorylated (activated) Akt1 (P < 0.05). CONCLUSION:The present study shows that supplementation of carnitine markedly decreases the expression of MuRF1 and concentrations of ubiquitinated proteins in skeletal muscle of rats, indicating a diminished degradation of myofibrillar proteins by the UPS. The study moreover shows that supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway which in turn might contribute to the observed down-regulation of MuRF1 and muscle protein ubiquitination.
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