l-carnitine is found in nearly all living cells. l-carnitine present in human body can be either ... more l-carnitine is found in nearly all living cells. l-carnitine present in human body can be either provided by a biosynthetic pathway or by food. Carnitine plays a major role in lipid and energy metabolism. In the human body, the primary role of l-carnitine is to shuttle long-chain fatty acids into the mitochondria where they are used to produce energy. l-carnitine is also involved in the peroxisomal oxidative metabolism and serves as a cofactor for various enzymatic reactions. Several reports suggest that l-carnitine may act as an anti-oxidant agent and limit the deleterious effects of free radicals. Many studies have estimated the role and the potential effectiveness of l-carnitine in various physiological and pathophysiological states such as physical exercise, heart disease, aging, weight management and brain function. A deficiency in l-carnitine has marked effects on the function of skeletal muscle, heart and nervous cells. Key Concepts: Carnitine is a cofactor for many enzymatic reactions. Carnitine regulates various physiological functions. Carnitine may limit ROS attack. Keywords: l-carnitine; lipid metabolism; mitochondria; peroxisome; muscle; physiology; nutrition
The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the que... more The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the question about the possible role of this enhancement in the hypolipidaemic effect of the drug and the underlying mechanisms. When fenofibrate was administered with mildronate (a gamma-butyrobetaine hydroxylase inhibitor) in suitable amount, the content in carnitine was found to be normalized in liver. However, triglyceride contents of liver and serum were then at least as low as in rats treated by fenofibrate only. When carnitine concentration was lowered by mildronate to the third of the normal value, a marked increase in triglycerides occurred both in liver and serum, while the five-fold increase in carnitine due to fenofibrate enhanced blood ketone body concentration with no effect on liver and serum triglycerides. Data suggest that the normal carnitine concentration is largely sufficient to meet the usual requirement for carnitine palmitoyltransferase I activity (CPT I). In rat liver, increase in mitochondrial CPT I activity and in peroxisomal fatty acid oxidation may constitute part of the hypolipidaemic effect of fenofibrate.
L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioav... more L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side effects, including induction of myopathy characterized by a metabolic mitochondria dysfunction and a diminution of the muscle L-carnitine content. In this study, we described the characteristics of L-carnitine transport in C2C12 cells. We also demonstrated that zidovudine inhibited the L-carnitine transporter. This inhibition led to a significant reduction of the muscle cell growth. In C2C12 cells, the supplementation of L-carnitine prevented the effects of zidovudine and restored the normal cell growth.
l-Carnitine is a vitamin-like nutrient essential for energy production and lipid metabolism in ma... more l-Carnitine is a vitamin-like nutrient essential for energy production and lipid metabolism in many organs and tissues such as skeletal muscle and heart. Even if l-carnitine can be synthesized, most of the carnitine present in human body is provided by food. Until now, no large study has been conducted where the content in l-carnitine of various foods was analyzed. The
Journal of Endocrinological Investigation, Apr 1, 2007
Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiolog... more Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation.
HAL (Le Centre pour la Communication Scientifique Directe), 2005
Experimental evidence indicates that n-3 fatty acids, especially the long-chain polyunsaturated f... more Experimental evidence indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids, unlike n-6 fatty acids could prevent cancer development. This survey shows that fatty acids could act through several mechanisms including the production of reactive oxygen species, the modulation of gene expression and signal transduction pathways, or the eicosanoid biosynthesis. Human genetics has underlined several polymorphisms in genes identified as possible targets of fatty acids which suggests that the link between nutritional intake and cancer prevention, especially the eventual anti-carcinogenic effects of n-3 fatty acids, depends on the genetic background. Further studies are needed to evaluate the effects of fatty acids on angiogenesis which represents a marker of a poor prognosis in cancer. Finally, the use of genomic technologies combined with nutritional strategies could provide a more understanding of the effects of n-3 fatty acid intake on cancer prevention.
The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting t... more The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability.
Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is... more Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is found in dairy and meat products, but is also biosynthesized from lysine and methionine via a process that, in rat, takes place essentially in the liver. After intestinal absorption or hepatic biosynthesis, carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle. In skeletal muscle, carnitine concentration was found to be 50 times higher than in the plasma, implicating an active transport system for carnitine. In this study, we characterized this transport in isolated rat myotubes, established mouse C2C12 myoblastic cells, and rat myotube plasma membranes and found that it was Na(+)-dependent and partly inhibited by a Na(+)/K(+) ATPase inhibitor. L-carnitine analogues such as D-carnitine and gamma-butyrobetaine interfere with this system as does acyl carnitine. Among these inhibitors, the most potent was mildronate (3-(2,2,2-trimethylhydrazinium)propionate), known as a gamma-butyrobetaine hydroxylase inhibitor. It also induced a marked decrease in carnitine transport into muscle cells. Removal of carnitine or treatment with mildronate induced growth inhibition of cultured C2C12 myoblastic cells. These data suggest that myoblast growth and/or differentiation is dependent upon the presence of carnitine.
Archives Des Maladies Professionnelles Et De L Environnement, Oct 1, 2020
Introduction L’Anses presente un etat des connaissances sur les dangers lies aux champs electroma... more Introduction L’Anses presente un etat des connaissances sur les dangers lies aux champs electromagnetiques basses frequences (CEM-BF) et les resultats de son expertise collective concernant les risques pour la sante lies aux expositions en milieu professionnel. Materiel et methodes Ce travail est fonde sur l’analyse des donnees de la litterature scientifique. Pour chaque effet sanitaire etudie, le niveau de preuve apporte par les donnees scientifiques a ete evalue en s’appuyant sur une methode adaptee au contexte des champs electromagnetiques. Resultats Toutes les professions peuvent etre exposees a des CEM-BF, mais a des intensites tres diverses. Ainsi, un photocopieur genere un champ magnetique avec une intensite maximale de 1,2 μT, un ecran d’ordinateur presente des emissions de l’ordre de 0,7 μT, alors qu’un poste de soudage peut generer des champs d’une intensite de 130 000 μT. Une etude menee conjointement par l’INRS et le centre de mesures physiques des Carsat/Cram a permis d’identifier et de recenser les principales familles d’equipements industriels emettant des rayonnements electromagnetiques, comme le soudage par resistance ou la magnetoscopie, dont les niveaux de champ magnetique peuvent dans certains cas depasser les valeurs limites reglementaires. Par ailleurs, des simulations numeriques menees sur des modeles humains realistes de femme enceinte ont montre que l’exposition induite chez le fœtus augmente avec le stade de la grossesse et peut etre superieure aux valeurs limites recommandees pour la population generale. Certaines etudes scientifiques ont montre une augmentation significative du risque de sclerose laterale amyotrophique chez les personnes exposees de facon professionnelle aux CEM-BF ou aux chocs electriques. Des recherches ont egalement ete menees sur la survenue de la maladie d’Alzheimer, de cancers et, chez la descendance des travailleurs exposes, de leucemie infantile. L’heterogeneite des resultats et les limites methodologiques des etudes ne permettent pas a ce jour de conclure a l’existence ou non d’un lien entre la survenue de ces pathologies et l’exposition professionnelle aux CEM-BF. Conclusion Les niveaux d’exposition aux champs magnetiques basses frequences parfois tres eleves en milieu professionnel et les incertitudes liees a la survenue de certains effets sanitaires ont conduit l’Anses a recommander aux employeurs, preventeurs, medecins du travail et services de sante au travail de mieux informer les femmes de l’existence de dispositions reglementaires qui prevoient l’amenagement de leur poste de travail lorsqu’elles sont enceintes, afin de limiter l’exposition du fœtus aux basses frequences.
l-carnitine is found in nearly all living cells. l-carnitine present in human body can be either ... more l-carnitine is found in nearly all living cells. l-carnitine present in human body can be either provided by a biosynthetic pathway or by food. Carnitine plays a major role in lipid and energy metabolism. In the human body, the primary role of l-carnitine is to shuttle long-chain fatty acids into the mitochondria where they are used to produce energy. l-carnitine is also involved in the peroxisomal oxidative metabolism and serves as a cofactor for various enzymatic reactions. Several reports suggest that l-carnitine may act as an anti-oxidant agent and limit the deleterious effects of free radicals. Many studies have estimated the role and the potential effectiveness of l-carnitine in various physiological and pathophysiological states such as physical exercise, heart disease, aging, weight management and brain function. A deficiency in l-carnitine has marked effects on the function of skeletal muscle, heart and nervous cells. Key Concepts: Carnitine is a cofactor for many enzymatic reactions. Carnitine regulates various physiological functions. Carnitine may limit ROS attack. Keywords: l-carnitine; lipid metabolism; mitochondria; peroxisome; muscle; physiology; nutrition
The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the que... more The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the question about the possible role of this enhancement in the hypolipidaemic effect of the drug and the underlying mechanisms. When fenofibrate was administered with mildronate (a gamma-butyrobetaine hydroxylase inhibitor) in suitable amount, the content in carnitine was found to be normalized in liver. However, triglyceride contents of liver and serum were then at least as low as in rats treated by fenofibrate only. When carnitine concentration was lowered by mildronate to the third of the normal value, a marked increase in triglycerides occurred both in liver and serum, while the five-fold increase in carnitine due to fenofibrate enhanced blood ketone body concentration with no effect on liver and serum triglycerides. Data suggest that the normal carnitine concentration is largely sufficient to meet the usual requirement for carnitine palmitoyltransferase I activity (CPT I). In rat liver, increase in mitochondrial CPT I activity and in peroxisomal fatty acid oxidation may constitute part of the hypolipidaemic effect of fenofibrate.
L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioav... more L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side effects, including induction of myopathy characterized by a metabolic mitochondria dysfunction and a diminution of the muscle L-carnitine content. In this study, we described the characteristics of L-carnitine transport in C2C12 cells. We also demonstrated that zidovudine inhibited the L-carnitine transporter. This inhibition led to a significant reduction of the muscle cell growth. In C2C12 cells, the supplementation of L-carnitine prevented the effects of zidovudine and restored the normal cell growth.
l-Carnitine is a vitamin-like nutrient essential for energy production and lipid metabolism in ma... more l-Carnitine is a vitamin-like nutrient essential for energy production and lipid metabolism in many organs and tissues such as skeletal muscle and heart. Even if l-carnitine can be synthesized, most of the carnitine present in human body is provided by food. Until now, no large study has been conducted where the content in l-carnitine of various foods was analyzed. The
Journal of Endocrinological Investigation, Apr 1, 2007
Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiolog... more Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation.
HAL (Le Centre pour la Communication Scientifique Directe), 2005
Experimental evidence indicates that n-3 fatty acids, especially the long-chain polyunsaturated f... more Experimental evidence indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids, unlike n-6 fatty acids could prevent cancer development. This survey shows that fatty acids could act through several mechanisms including the production of reactive oxygen species, the modulation of gene expression and signal transduction pathways, or the eicosanoid biosynthesis. Human genetics has underlined several polymorphisms in genes identified as possible targets of fatty acids which suggests that the link between nutritional intake and cancer prevention, especially the eventual anti-carcinogenic effects of n-3 fatty acids, depends on the genetic background. Further studies are needed to evaluate the effects of fatty acids on angiogenesis which represents a marker of a poor prognosis in cancer. Finally, the use of genomic technologies combined with nutritional strategies could provide a more understanding of the effects of n-3 fatty acid intake on cancer prevention.
The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting t... more The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability.
Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is... more Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is found in dairy and meat products, but is also biosynthesized from lysine and methionine via a process that, in rat, takes place essentially in the liver. After intestinal absorption or hepatic biosynthesis, carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle. In skeletal muscle, carnitine concentration was found to be 50 times higher than in the plasma, implicating an active transport system for carnitine. In this study, we characterized this transport in isolated rat myotubes, established mouse C2C12 myoblastic cells, and rat myotube plasma membranes and found that it was Na(+)-dependent and partly inhibited by a Na(+)/K(+) ATPase inhibitor. L-carnitine analogues such as D-carnitine and gamma-butyrobetaine interfere with this system as does acyl carnitine. Among these inhibitors, the most potent was mildronate (3-(2,2,2-trimethylhydrazinium)propionate), known as a gamma-butyrobetaine hydroxylase inhibitor. It also induced a marked decrease in carnitine transport into muscle cells. Removal of carnitine or treatment with mildronate induced growth inhibition of cultured C2C12 myoblastic cells. These data suggest that myoblast growth and/or differentiation is dependent upon the presence of carnitine.
Archives Des Maladies Professionnelles Et De L Environnement, Oct 1, 2020
Introduction L’Anses presente un etat des connaissances sur les dangers lies aux champs electroma... more Introduction L’Anses presente un etat des connaissances sur les dangers lies aux champs electromagnetiques basses frequences (CEM-BF) et les resultats de son expertise collective concernant les risques pour la sante lies aux expositions en milieu professionnel. Materiel et methodes Ce travail est fonde sur l’analyse des donnees de la litterature scientifique. Pour chaque effet sanitaire etudie, le niveau de preuve apporte par les donnees scientifiques a ete evalue en s’appuyant sur une methode adaptee au contexte des champs electromagnetiques. Resultats Toutes les professions peuvent etre exposees a des CEM-BF, mais a des intensites tres diverses. Ainsi, un photocopieur genere un champ magnetique avec une intensite maximale de 1,2 μT, un ecran d’ordinateur presente des emissions de l’ordre de 0,7 μT, alors qu’un poste de soudage peut generer des champs d’une intensite de 130 000 μT. Une etude menee conjointement par l’INRS et le centre de mesures physiques des Carsat/Cram a permis d’identifier et de recenser les principales familles d’equipements industriels emettant des rayonnements electromagnetiques, comme le soudage par resistance ou la magnetoscopie, dont les niveaux de champ magnetique peuvent dans certains cas depasser les valeurs limites reglementaires. Par ailleurs, des simulations numeriques menees sur des modeles humains realistes de femme enceinte ont montre que l’exposition induite chez le fœtus augmente avec le stade de la grossesse et peut etre superieure aux valeurs limites recommandees pour la population generale. Certaines etudes scientifiques ont montre une augmentation significative du risque de sclerose laterale amyotrophique chez les personnes exposees de facon professionnelle aux CEM-BF ou aux chocs electriques. Des recherches ont egalement ete menees sur la survenue de la maladie d’Alzheimer, de cancers et, chez la descendance des travailleurs exposes, de leucemie infantile. L’heterogeneite des resultats et les limites methodologiques des etudes ne permettent pas a ce jour de conclure a l’existence ou non d’un lien entre la survenue de ces pathologies et l’exposition professionnelle aux CEM-BF. Conclusion Les niveaux d’exposition aux champs magnetiques basses frequences parfois tres eleves en milieu professionnel et les incertitudes liees a la survenue de certains effets sanitaires ont conduit l’Anses a recommander aux employeurs, preventeurs, medecins du travail et services de sante au travail de mieux informer les femmes de l’existence de dispositions reglementaires qui prevoient l’amenagement de leur poste de travail lorsqu’elles sont enceintes, afin de limiter l’exposition du fœtus aux basses frequences.
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