title: Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12.
abstract: Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors.
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany. Electronic address: Dorothe.J.Deusing@ernaehrung.uni-giessen.de.
authors.forename: Dorothé Jenni
authors.initials: DJ
authors.lastname: Deusing
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany. Electronic address: m.beyrer@web.de.
authors.forename: Melanie
authors.initials: M
authors.lastname: Beyrer
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany. Electronic address: Elena.Fitzenberger@ernaehrung.uni-giessen.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Fitzenberger
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany. Electronic address: uwe.wenzel@ernaehrung.uni-giessen.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Wenzel
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002331:Carnitine / Q000494:pharmacology*; D017931:DNA Primers; D005947:Glucose / Q000008:administration & dosage*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D017931:DNA Primers; D018160:Receptors, Cytoplasmic and Nuclear; D005947:Glucose; D002331:Carnitine
keywords: Caenorhabditis elegans; Carnitine; Glucose-induced toxicity; Lysosomes; Proteasome; Survival