Carnitine

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Carnitine

  • free carnitine

  • Terms modified by Carnitine

  • carnitine deficiency
  • carnitine level
  • carnitine palmitoyl transferase
  • carnitine supplement
  • carnitine supplementation
  • carnitine transport
  • carnitine transporter
  • carnitine uptake

  • Selected Abstracts


    OCTN2 is associated with carnitine transport capacity of rat skeletal muscles

    ACTA PHYSIOLOGICA, Issue 1 2010
    Y. Furuichi
    Abstract Aim:, Carnitine plays an essential role in fat oxidation in skeletal muscles; therefore carnitine influx could be crucial for muscle metabolism. OCTN2, a sodium-dependent solute carrier, is assumed to transport carnitine into various organs. However, OCTN2 protein expression and the functional importance of carnitine transport for muscle metabolism have not been studied. We tested the hypothesis that OCTN2 is expressed at higher levels in oxidative muscles than in other muscles, and that the carnitine uptake capacity of skeletal muscles depends on the amount of OCTN2. Methods:, Rat hindlimb muscles (soleus, plantaris, and the surface and deep portions of gastrocnemius) were used for Western blotting to detect OCTN2. Tissue carnitine uptake was examined by an integration plot analysis using l -[3H]carnitine as a tracer. Tissue carnitine content was determined by enzymatic cycling methods. The percentage of type I fibres was determined by histochemical analysis. Results:, OCTN2 was detected in all skeletal muscles although the amount was lower than that in the kidney. OCTN2 expression was significantly higher in soleus than in the other skeletal muscles. The amount of OCTN2 was positively correlated with the percentage of type I fibres in hindlimb muscles. The integration plot analysis revealed a positive correlation between the uptake clearance of l -[3H]carnitine and the amount of OCTN2 in skeletal muscles. However, the carnitine content in soleus was lower than that in other skeletal muscles. Conclusion:, OCTN2 is functionally expressed in skeletal muscles and is involved in the import of carnitine for fatty acid oxidation, especially in highly oxidative muscles. [source]


    Carnitine Palmityltransferase II (CPT2) Deficiency and Migraine Headache: Two Case Reports

    HEADACHE, Issue 5 2003
    Marielle A. Kabbouche MD
    Background.,Migraine headache is common and has multiple etiologies. A number of mitochondrial anomalies have been described for migraine, and mitochondrial dysfunction has been implicated as one potential pathophysiological mechanism. Carnitine is used by mitochondria for fatty acid transportation; its deficiency, however, has not been implicated in migraine pathophysiology. Methods and Results.,Two adolescent girls presented to the Headache Center at Cincinnati Children's Hospital Medical Center with frequent headaches and were diagnosed with migraine by the International Headache Society (IHS) criteria. Both girls had a history of recurrent fatigue, muscle cramps, and multiple side effects from their prophylactic treatment. Carnitine levels were measured and found to be low. Carnitine supplementation was initiated. Both patients had a reduction in headache frequency, as well as an improvement in their associated symptoms and other complaints. A skin and muscle biopsy obtained from one patient revealed a partial carnitine palmityltransferase II deficiency in the muscle only. Conclusion.,Carnitine palmityltransferase II deficiency may represent another etiology for migraine headache, and may be useful in further defining the pathophysiology of migraine. When properly recognized, supplementation with carnitine may improve the outcome of the migraine as well as the carnitine-associated symptoms. [source]


    Does l -carnitine have any effect on cold preservation injury of non-fatty liver in the University of Wisconsin solution?

    HEPATOLOGY RESEARCH, Issue 8 2007
    Abdurrahman Coskun
    Aim:, To evaluate the protective effect of l -carnitine on liver tissue preserved in University of Wisconsin (UW) solution. Methods:, Twenty Wistar Albino rats were divided into two groups, a control (UW) group and a UW plus l -carnitine group. Retrieved liver grafts were preserved in UW and UW plus l -carnitine solutions at +4°C. Preservation solution samples were assessed at 2, 24, 36, and 48 h to measure alanine aminotransferase and acid phosphatase activity. Tissue injury was scored on paraffin sections. Results:, No micro or macrovacuolar fat droplets were observed in the tissue slices. l -Carnitine effectively decreased enzyme release when added to UW solution (P < 0.05). Conclusion:, In addition to fatty liver, l -carnitine might be a metabolic adjunct in preservation solutions for non-fatty liver within UW solution. [source]


    L -Carnitine in the treatment of HIV-associated lipodystrophy syndrome

    HIV MEDICINE, Issue 1 2001
    S Mauss
    Summary The objective of this pilot study was to assess the effect of L -carnitine on the course of the HIV-associated lipodystrophy syndrome. Twelve patients presenting with combined atrophic and hypertrophic changes of body fat were treated with L -carnitine 1000 mg bid for 3 months. No marked improvement of the body changes was observed. However a reduction in serum cholesterol levels, but not triglycerides, was noted. These preliminary data do not support the use of L -carnitine for the rapid reversal of advanced fat tissue alterations due to HIV-associated lipodystrophy. [source]


    Chemical form of dietary l -Carnitine affects plasma but not tissue Carnitine concentrations in male Sprague,Dawley rats

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2009
    B. D. Lambert
    Summary In Experiment 1, rats (n = 54) were randomly assigned to control or one of the four sources of l -Carnitine supplemented at either 100 or 200 ,mol/kg/day and were allowed to acclimate for 14 days. Following a 12-h fast, plasma samples were obtained at 0, 5, 10, 15, 30, 60, 120, 240, 480 and 720 min after l -Carnitine feeding and assayed for free l -Carnitine concentration. Plasma-free l -Carnitine levels were affected by time after treatment intake (p < 0.0001) and l -Carnitine source (p < 0.0001). The time × source interaction was not statistically significant (p = 0.99). In Experiment 2, rats (n = 54) were randomly assigned to control or one of the four sources of l -Carnitine at either 100 or 200 ,mol/kg/day and were acclimated as in experiment 1. Rats were sacrificed 120 min after feeding. Samples of liver and skeletal muscle were obtained and assayed for free l -Carnitine concentration. Neither skeletal muscle (p = 0.44) or liver (p = 0.59) tissue concentrations of l -Carnitine were affected by any l -Carnitine source as compared with the control. We conclude that some differences exist in plasma concentrations of free l -Carnitine following ingestion of different chemical forms of l -Carnitine. It is unclear if these differences in the circulating concentration of free l -Carnitine translate into any physiological differences for the animal. In this study, chemical form of l -Carnitine had no effect on skeletal muscle or liver tissue concentrations of l -Carnitine in young male Wistar rats. [source]


    Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood,brain barrier

    JOURNAL OF NEUROCHEMISTRY, Issue 1 2008
    Dorota Miecz
    Abstract Carnitine ,-hydroxy-,-(trimethylammonio)butyrate , a compound necessary in the peripheral tissues for a transfer of fatty acids for their oxidation within the cell, accumulates in the brain despite low ,-oxidation in this organ. In order to enter the brain, carnitine has to cross the blood,brain barrier formed by capillary endothelial cells which are in close interaction with astrocytes. Previous studies, demonstrating expression of mRNA coding two carnitine transporters , organic cation/carnitine transporter 2 (OCTN2) and B0,+ in endothelial cells, did not give any information on carnitine transporters polarity in endothelium. Therefore more detailed experiments were performed on expression and localization of a high affinity carnitine transporter OCTN2 in an in vitro model of the blood,brain barrier by real-time PCR, western blot analysis, and immunocytochemistry. The amount of mRNA was comparable in endothelial cells and kidney, when referred to house-keeping genes, it was, however, significantly lower in astrocytes. Polarity of OCTN2 localization was further studied in an in vitro model of the blood,brain barrier with use of anti-OCTN2 antibodies. Z -axis analysis of the confocal microscope pictures of endothelial cells, with anti-P-glycoprotein antibodies as the marker of apical membrane, showed OCTN2 localization at the basolateral membrane and in the cytoplasmic region in the vicinity of nuclei. Localization of OCTN2 suggest that carnitine can be also transported from the brain, playing an important role in removal of certain acyl esters. [source]


    Acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in human immunodeficiency virus patients: an open label study

    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2006
    Maurizio Osio
    Abstract Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus (HIV) patients under dideoxynucleoside therapy, benefits only partially from medical therapy, and often leads to drug discontinuation. Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism, eventually related to a reduction of mitochondrial DNA content, and interference with nerve growth factor activity. Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions. Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation. The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients. Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period. Efficacy was evaluated by means of the modified Short Form McGill Pain Questionnaire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit. Mean pain intensity score was significantly reduced during the study, changing from 7.35 ± 1.98 (mean ± SD) at baseline to 5.80 ± 2.63 at week 4 (p = 0.0001). Electrophysiological parameters did not significantly change between baseline and week 4. In this study, acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity. On the contrary, no effect was noted on neurophysiological parameters. [source]


    Plasma and liver carnitine status of children with chronic liver disease and cirrhosis

    PEDIATRICS INTERNATIONAL, Issue 4 2001
    Mukadder A Selimo
    AbstractBackground: Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane for oxidation. As its synthesis is performed in the liver, alterations in carnitine metabolism is expected in liver diseases, especially in cirrhosis. Methods: In this study, we investigated plasma and liver carnitine concentrations of 68 children with chronic liver disease, 36 of whom had cirrhosis as well. Carnitine level was determined by enzymatic method. Results: Plasma and liver carnitine concentrations were not correlated. Mean plasma carnitine level of cirrhotic children was significantly lower than that of the control group (P<0. 0001). While there was no difference between liver carnitine concentrations of children with chronic liver disease and cirrhosis (P>0.05), mean plasma level of cirrhotics were lower (P<0.05). Plasma carnitine was correlated with albumin, triglyceride and gamma glutamyl transpeptidase (GGT) in patients with chronic liver disease (P<0.05). Liver carnitine was correlated with GGT in cirrhotic patients (P<0.005). Children with malnutrition had higher plasma and liver carnitine levels (P<0.05). The highest plasma and liver carnitine levels were detected in children with biliary atresia and criptogenic cirrhosis, respectively. Both the lowest plasma and liver carnitine levels were detected in Wilson's disease. Conclusion: Children with cirrhosis have low plasma carnitine concentrations. This finding is prominent in children with Wilson's disease. As carnitine is an essential factor in lipid metabolism, the carnitine supplementation for patients with cirrhosis in childhood, especially with Wilson's disease, seems to be mandatory. [source]


    Plasma carnitine levels in children with down syndrome,

    AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 6 2001
    Mehmet Seven
    Carnitine is responsible for several chemical processes, including lipid metabolism, nerve cell conduction, reduction in muscle hypotonia, and limitation in oxidative damage to cells. In patients with Down syndrome (DS), the process of growth is behind that of normal children and neuromuscular control is attained somewhat later. The purpose of this study was to assess variation in levels of carnitine in normal and DS children and the relationship between the amount of carnitine and age. The study involved 30 (15 girls, 15 boys) normal children and 40 (20 girls, 20 boys) DS patients of Turkish ancestry, 6 months to 13 years of age. Carnitine level was determined using Deufel's enzymatic method. Carnitine level was significantly lower in DS patients compared with normal children between 6 months to 5 years of age. Between 5 and 13 years of age, the level of carnitine was about the same in both the normal and DS groups. The results suggest that carnitine level shows a different pattern of age related increase in DS compared to normal children. Am. J. Hum. Biol. 13:721,725, 2001. Published 2001 Wiley-Liss, Inc. [source]


    Disorders of carnitine transport and the carnitine cycle,

    AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2006
    Nicola Longo
    Abstract Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta oxidation (carnitine palmitoyl transferase 2, CPT2). Deficiency of the OCTN2 carnitine transporter causes primary carnitine deficiency, characterized by increased losses of carnitine in the urine and decreased carnitine accumulation in tissues. Patients can present with hypoketotic hypoglycemia and hepatic encephalopathy, or with skeletal and cardiac myopathy. This disease responds to carnitine supplementation. Defects in the liver isoform of CPT1 present with recurrent attacks of fasting hypoketotic hypoglycemia. The heart and the muscle, which express a genetically distinct form of CPT1, are usually unaffected. These patients can have elevated levels of plasma carnitine. CACT deficiency presents in most cases in the neonatal period with hypoglycemia, hyperammonemia, and cardiomyopathy with arrhythmia leading to cardiac arrest. Plasma carnitine levels are extremely low. Deficiency of CPT2 present more frequently in adults with rhabdomyolysis triggered by prolonged exercise. More severe variants of CPT2 deficiency present in the neonatal period similarly to CACT deficiency associated or not with multiple congenital anomalies. Treatment for deficiency of CPT1, CPT2, and CACT consists in a low-fat diet supplemented with medium chain triglycerides that can be metabolized by mitochondria independently from carnitine, carnitine supplements, and avoidance of fasting and sustained exercise. © 2006 Wiley-Liss, Inc. [source]


    Upstream genetic variant near INSIG2, influences response to carnitine supplementation in bipolar patients with valproate-induced weight gain

    ACTA NEUROPSYCHIATRICA, Issue 3 2009
    K Doudney
    Background: The protein product of INSIG2 is involved in cholesterol and triglyceride metabolism and homeostasis. Variation at rs7566605 near the gene INSIG2 has been associated with increased BMI. Objective: To evaluate the effect of rs7566605/INSIG2 genotype on the ability of valproate-treated bipolar patients (BMI , 25 kg/m2) to lose weight using carnitine supplementation during a 26-week lifestyle intervention study. Design: Forty-eight bipolar patients with clinically significant treatment emergent weight gain were genotyped at the rs7566605 SNP. Participants were randomised to l -carnitine (15 mg/kg/day) or placebo for 26 weeks in conjunction with a moderately energy restricted, low-fat diet. Weight and body fat percent were measured fortnightly. Waist circumference measurements and dual-energy X-ray absorptiometry were used to assess changes in body composition. Obesity-related biomarkers were measured at baseline and 26 weeks. Results: There was a significant interaction between rs7566605/INSIG2 genetic status and treatment with carnitine or placebo. Carnitine had no significant effect on body composition measures in G allele homozygous patients who lost between 0.97 and 2.23 kg of fat. However C allele carriers on average gained 2.28 kg when given a placebo. Carnitine supplementation in this group enabled average weight loss of 2.22 kg of fat (p = 0.01). Approximately half of this mass was in the vital truncal compartment (p = 0.002). Bioinformatic analysis detected that the SNP lies in a highly conserved 336 bp sequence which potentially affects INSIG2 gene expression. Conclusions: C-carriers at rs7566605, possibly regulating the homeostasis gene INSIG2, lost significantly less weight in this lifestyle intervention study. This effect was reversed by carnitine supplementation. [source]


    ChemInform Abstract: Efficient Enantioselective Synthesis of (R)-(-)-Carnitine from Glycerol.

    CHEMINFORM, Issue 7 2001
    Mauro Marzi
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


    OCTN2 is associated with carnitine transport capacity of rat skeletal muscles

    ACTA PHYSIOLOGICA, Issue 1 2010
    Y. Furuichi
    Abstract Aim:, Carnitine plays an essential role in fat oxidation in skeletal muscles; therefore carnitine influx could be crucial for muscle metabolism. OCTN2, a sodium-dependent solute carrier, is assumed to transport carnitine into various organs. However, OCTN2 protein expression and the functional importance of carnitine transport for muscle metabolism have not been studied. We tested the hypothesis that OCTN2 is expressed at higher levels in oxidative muscles than in other muscles, and that the carnitine uptake capacity of skeletal muscles depends on the amount of OCTN2. Methods:, Rat hindlimb muscles (soleus, plantaris, and the surface and deep portions of gastrocnemius) were used for Western blotting to detect OCTN2. Tissue carnitine uptake was examined by an integration plot analysis using l -[3H]carnitine as a tracer. Tissue carnitine content was determined by enzymatic cycling methods. The percentage of type I fibres was determined by histochemical analysis. Results:, OCTN2 was detected in all skeletal muscles although the amount was lower than that in the kidney. OCTN2 expression was significantly higher in soleus than in the other skeletal muscles. The amount of OCTN2 was positively correlated with the percentage of type I fibres in hindlimb muscles. The integration plot analysis revealed a positive correlation between the uptake clearance of l -[3H]carnitine and the amount of OCTN2 in skeletal muscles. However, the carnitine content in soleus was lower than that in other skeletal muscles. Conclusion:, OCTN2 is functionally expressed in skeletal muscles and is involved in the import of carnitine for fatty acid oxidation, especially in highly oxidative muscles. [source]


    Effects of Valproate on Acylcarnitines in Children with Epilepsy Using ESI-MS/MS

    EPILEPSIA, Issue 1 2007
    Tamara Werner
    Summary:,Purpose: To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy. Methods: Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines in children under VPA treatment without pretreatment (group 1) or with pretreatment with other antiepileptic drugs (group 2) before the start of VPA treatment at an early and a late treatment interval (12,66, 90,260 days after the beginning of treatment, respectively). Cross-sectional comparison of these two VPA groups and of a group receiving carbamazepine monotherapy (group 3) with controls. Results: Acylcarnitines in epileptic patients before VPA therapy did not differ from control values. In group 1, decreases of C0 (,26%), C2 (,12%), C16 (,31%), C18 (,41%), Ctotal (,10%), increases of C5OH (+31%), C8 (+33%) in the early treatment interval, and decreases of C16 (,21%), C18 (,42%), and increases of C2 (+26%), C5OH (+44%) in the late treatment interval were significant. In group 2, both in the longitudinal and the cross-sectional study, only a decrease of C18 (,41%, ,43%, respectively) in the late treatment interval was found. In group 3, no significant changes have been observed. Conclusions: We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy. The treatment interval with the most marked changes coincides with the interval of highest risk for VPA-induced hepatotoxicity. The observed specific acylcarnitine pattern might point to the impaired intermediary metabolism that is responsible for VPA-induced hepatotoxicity. [source]


    Interaction between Anticonvulsants and Human Placental Carnitine Transporter

    EPILEPSIA, Issue 3 2004
    Shu-Pei Wu
    Summary: Purpose: To examine the inhibitory effect of anticonvulsants (AEDs) on carnitine transport by the human placental carnitine transporter. Methods: Uptake of radiolabeled carnitine by human placental brush-border membrane vesicles was measured in the absence and presence of tiagabine (TGB), vigabatrin (VGB), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), valproic acid (VPA), and phenytoin (PHT). The mechanism of the inhibitory action of TGB was determined. Results: Most of the AEDs inhibited placental carnitine transport. Kinetic analyses showed that TGB had the greatest inhibitory effect [50% inhibitory concentration (IC50, 190 ,M)], and the order of inhibitory potency was TGB > PHT > GBP > VPA > VGB, TPM > LTG. Further studies showed that TGB competitively inhibited carnitine uptake by the human placental carnitine transporter, suggesting that it may be a substrate for this carrier. Conclusions: Although the involvement of carnitine deficiency in fetal anticonvulsant syndrome requires further evaluation, potential interference with placental carnitine transport by several AEDs was demonstrated. Despite the higher inhibitory potency of TGB, given the therapeutic unbound concentrations, the results for VPA and PHT are probably more clinically significant. [source]


    Peroxisome proliferator-activated receptor ,,retinoid X receptor agonists induce beta-cell protection against palmitate toxicity

    FEBS JOURNAL, Issue 23 2007
    Karine Hellemans
    Fatty acids can stimulate the secretory activity of insulin-producing beta-cells. At elevated concentrations, they can also be toxic to isolated beta-cells. This toxicity varies inversely with the cellular ability to accumulate neutral lipids in the cytoplasm. To further examine whether cytoprotection can be achieved by decreasing cytoplasmic levels of free acyl moieties, we investigated whether palmitate toxicity is also lowered by stimulating its ,-oxidation. Lower rates of palmitate-induced beta-cell death were measured in the presence of l -carnitine as well as after addition of peroxisome proliferator-activated receptor , (PPAR,) agonists, conditions leading to increased palmitate oxidation. In contrast, inhibition of mitochondrial ,-oxidation by etomoxir increased palmitate toxicity. A combination of PPAR, and retinoid X receptor (RXR) agonists acted synergistically and led to complete protection; this was associated with enhanced expression levels of genes involved in mitochondrial and peroxisomal ,-oxidation, lipid metabolism, and peroxisome proliferation. PPAR,,RXR protection was abolished by the carnitine palmitoyl transferase 1 inhibitor etomoxir. These observations indicate that PPAR, and RXR regulate beta-cell susceptibility to long-chain fatty acid toxicity by increasing the rates of ,-oxidation and by involving peroxisomes in fatty acid metabolism. [source]


    Development and characterization of an animal model of carnitine deficiency

    FEBS JOURNAL, Issue 6 2001
    Markus Spaniol
    Mammals cover their carnitine needs by diet and biosynthesis. The last step of carnitine biosynthesis is the conversion of butyrobetaine to carnitine by butyrobetaine hydroxylase. We investigated the effect of N -trimethyl-hydrazine-3-propionate (THP), a butyrobetaine analogue, on butyrobetaine hydroxylase kinetics, and carnitine biosynthesis and body homeostasis in rats fed a casein-based or a vegetarian diet. The Km of butyrobetaine hydroxylase purified from rat liver was 41 ± 9 µmol·L,1 for butyrobetaine and 37 ± 5 µmol·L,1 for THP, and THP was a competitive inhibitor of butyrobetaine hydroxylase (Ki 16 ± 2 µmol·L,1). In rats fed a vegetarian diet, renal excretion of total carnitine was increased by THP (20 mg·100 g,1·day,1 for three weeks), averaging 96 ± 36 and 5.3 ± 1.2 µmol·day,1 in THP-treated and control rats, respectively. After three weeks of treatment, the total carnitine plasma concentration (8.8 ± 2.1 versus 52.8 ± 11.4 µmol·L,1) and tissue levels were decreased in THP-treated rats (liver 0.19 ± 0.03 versus 0.59 ± 0.08 and muscle 0.24 ± 0.04 versus 1.07 ± 0.13 µmol·g,1). Carnitine biosynthesis was blocked in THP-treated rats (,0.22 ± 0.13 versus 0.57 ± 0.21 µmol·100 g,1·day,1). Similar results were obtained in rats treated with the casein-based diet. THP inhibited carnitine transport by rat renal brush-border membrane vesicles competitively (Ki 41 ± 3 µmol·L,1). Palmitate metabolism in vivo was impaired in THP-treated rats and the livers showed mixed steatosis. Steady-state mRNA levels of the carnitine transporter rat OCTN2 were increased in THP-treated rats in skeletal muscle and small intestine. In conclusion, THP inhibits butyrobetaine hydroxylase competitively, blocks carnitine biosynthesis in vivo and interacts competitively with renal carnitine reabsorption. THP-treated rats develop systemic carnitine deficiency over three weeks and can therefore serve as an animal model for human carnitine deficiency. [source]


    Acetyl- l -carnitine improves aged brain function

    GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2010
    Satoru Kobayashi
    The effects of acetyl- l -carnitine (ALCAR), an acetyl derivative of l -carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb,Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S99,S106. [source]


    Carnitine Palmityltransferase II (CPT2) Deficiency and Migraine Headache: Two Case Reports

    HEADACHE, Issue 5 2003
    Marielle A. Kabbouche MD
    Background.,Migraine headache is common and has multiple etiologies. A number of mitochondrial anomalies have been described for migraine, and mitochondrial dysfunction has been implicated as one potential pathophysiological mechanism. Carnitine is used by mitochondria for fatty acid transportation; its deficiency, however, has not been implicated in migraine pathophysiology. Methods and Results.,Two adolescent girls presented to the Headache Center at Cincinnati Children's Hospital Medical Center with frequent headaches and were diagnosed with migraine by the International Headache Society (IHS) criteria. Both girls had a history of recurrent fatigue, muscle cramps, and multiple side effects from their prophylactic treatment. Carnitine levels were measured and found to be low. Carnitine supplementation was initiated. Both patients had a reduction in headache frequency, as well as an improvement in their associated symptoms and other complaints. A skin and muscle biopsy obtained from one patient revealed a partial carnitine palmityltransferase II deficiency in the muscle only. Conclusion.,Carnitine palmityltransferase II deficiency may represent another etiology for migraine headache, and may be useful in further defining the pathophysiology of migraine. When properly recognized, supplementation with carnitine may improve the outcome of the migraine as well as the carnitine-associated symptoms. [source]


    Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis

    HEPATOLOGY, Issue 4 2003
    M.D., Mercedes Pérez-Carreras Ph.D.
    Mitochondrial dysfunction might play a central role in the pathogenesis of nonalcoholic steatohepatits (NASH). The aims of this study were to evaluate whether free fatty acid (FFA) transport into the mitochondria or the activity of mitochondria respiratory chain (MRC) complexes are impaired in NASH. In patients with NASH and control subjects, we measured free carnitine, short-chain acylcarnitine (SCAC) and long-chain acylcarnitine (LCAC) esters, carnitine palmitoyltransferase (CPT) activity, and MRC enzyme activity in liver tissue as well as serum concentration of tumor necrosis factor , (TNF-,), homeostatic metabolic assessment of insulin resistance (HOMAIR), and body mass index (BMI). In patients with NASH, the LCAC/free carnitine ratio was significantly increased and the SCAC/free carnitine ratio was decreased. In patients with NASH, the activity of the MRC complexes was decreased to 63% ± 20% (complex I), 58.5% ± 16.7% (complex II), 70.6% ± 10.3% (complex III), 62.5% ± 13% (complex IV), and 42.4% ± 9.1% (adenosine triphosphate synthase) of the corresponding control values. Activity of these complexes correlated significantly with serum TNF-, and HOMAIR. Serum TNF-, (36.3 ± 23.1 pg/mL), HOMAIR (4.5 ± 2.38), and BMI (29.9 ± 3.5 kg/m2) values were significantly increased in patients with NASH. In conclusion, activities of MRC complexes were decreased in liver tissue of patients with NASH. This dysfunction correlated with serum TNF-,, insulin resistance, and BMI values. (Hepatology 2003;38:999,1007). [source]


    Does l -carnitine have any effect on cold preservation injury of non-fatty liver in the University of Wisconsin solution?

    HEPATOLOGY RESEARCH, Issue 8 2007
    Abdurrahman Coskun
    Aim:, To evaluate the protective effect of l -carnitine on liver tissue preserved in University of Wisconsin (UW) solution. Methods:, Twenty Wistar Albino rats were divided into two groups, a control (UW) group and a UW plus l -carnitine group. Retrieved liver grafts were preserved in UW and UW plus l -carnitine solutions at +4°C. Preservation solution samples were assessed at 2, 24, 36, and 48 h to measure alanine aminotransferase and acid phosphatase activity. Tissue injury was scored on paraffin sections. Results:, No micro or macrovacuolar fat droplets were observed in the tissue slices. l -Carnitine effectively decreased enzyme release when added to UW solution (P < 0.05). Conclusion:, In addition to fatty liver, l -carnitine might be a metabolic adjunct in preservation solutions for non-fatty liver within UW solution. [source]


    L -Carnitine in the treatment of HIV-associated lipodystrophy syndrome

    HIV MEDICINE, Issue 1 2001
    S Mauss
    Summary The objective of this pilot study was to assess the effect of L -carnitine on the course of the HIV-associated lipodystrophy syndrome. Twelve patients presenting with combined atrophic and hypertrophic changes of body fat were treated with L -carnitine 1000 mg bid for 3 months. No marked improvement of the body changes was observed. However a reduction in serum cholesterol levels, but not triglycerides, was noted. These preliminary data do not support the use of L -carnitine for the rapid reversal of advanced fat tissue alterations due to HIV-associated lipodystrophy. [source]


    Evolution of blood parameters during weight loss in experimental obese Beagle dogs

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2004
    M. Diez
    Summary The effects of weight loss on hormonal and biochemical blood parameters were measured monthly [carnitine, creatinine, urea, free T4 (fT4), total T4 (TT4), plasma alkaline phosphatases (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), potassium and total proteins] or bimonthly [cholesterol, triglycerides, non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I), glucose, insulin] in eight obese Beagles dogs fed either a high protein dry diet, DP (crude protein 47.5%, on dry matter basis) or a commercial high fibre diet, HF (crude protein 23.8%, crude fibre 23.3%). The dogs were allotted to two groups according to sex and body weight (BW) and they were respectively fed with the DP or the control HF diet during 12,26 weeks, until they reach their optimal BW. The plasma basal triglycerides and cholesterol concentrations were decreased by the two diets but the difference was only significant for the DP diet. The plasma mean NEFA concentration increased regularly over the period with the HF diet, without significant difference between the two diets. No effect of diet or weight loss was observed on plasma carnitine, urea, creatinine, ALP, AST, ALT, potassium, TT4, FT4, IGF-I, glucose and insulin. Weight loss induced a decrease in fT4 plasma concentration (p < 0.001). The high protein diet allowed a safe weight loss. [source]


    Effect of L -carnitine supplementation on performance parameters in gilts and sows

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2001
    K. Eder
    The effect of L-carnitine supplementation during pregnancy and lactation on performance parameters of sows was studied. The trial comprised a total of 127 sows (40 gilts, 87 mature sows) which were divided into a control and a treatment group. All animals were fed individually and received basic feed mixtures for pregnancy and lactation with low carnitine concentrations (gestation diet: 4.7 mg/kg feed, lactation diet: 12.5 mg/kg feed). The rations of the sows in the treated group were supplemented with 125 mg L -carnitine per head and day during pregnancy and 250 mg L -carnitine per head and day during lactation. The animals of the control group received identical feed mixtures in identical amounts, but without the L -carnitine supplement. L -carnitine supplementation resulted in higher sow liveweight gains between day 1 and day 85 of pregnancy. The number of piglets per litter and the number born alive did not differ between the control sows and those treated with L -carnitine. However, the L -carnitine-supplemented sows produced only half as many non-viable piglets as the control animals. Moreover, litter weight and mean birth weight of piglets from L -carnitine-treated sows were higher than in the control sows. This effect was more marked in gilts (+8% higher litter weight, +9% higher piglet weight) than in sows (+7% and +6%, respectively). Piglets from sows whose ration was supplemented with L -carnitine showed higher liveweight gains during the suckling period (+12% for gilts, +4% for sows), which is why litter weights post weaning were also higher among the sows treated with L -carnitine than in the control sows (+14% for gilts, +10% for sows). Overall, the study shows that dietary supplementation with L -carnitine during pregnancy and lactation improves the reproductive performance of sows. [source]


    l -carnitine supplementation and lipid metabolism of rats fed a hyperlipidaemic diet

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2000
    K. Eder
    Summary Until now, there has been no clear knowledge about the effect of dietary carnitine supplementation on lipid metabolism. Therefore, this study was conducted to investigate the effect of a dietary l -carnitine supplementation (500 mg/kg) onx the lipid metabolism of adult rats. Rats fed a hyperlipidaemic basal diet containing 15% lard and 1% cholesterol were used as an animal model. The feeding period was 6 weeks. As parameters of lipid metabolism, the concentrations of individual lipids in plasma, lipoproteins and liver and the fatty acid composition of liver and erythrocyte total lipids were determined. There were no significant differences between the control group and the group receiving the diet supplemented with carnitine on parameters of animal performance (daily body weight gains and feed conversion ratio). As expected, plasma, very low-density lipoproteins (VLDL) and liver exhibited high concentrations of cholesterol. Concentrations of triglycerides and phospholipids in plasma and individual lipoproteins as well as the concentrations of triglycerides, cholesterol and phospholipids in the liver were not significantly altered by dietary carnitine supplementation. The concentration of cholesterol in plasma and liver was increased by dietary carnitine. The fatty acid composition of liver and erythrocyte total lipids was not influenced by dietary carnitine supplementation. In conclusion, this study does not indicate a lipid-lowering effect of dietary carnitine supplementation in hyperlipidaemic rats. Probably, the essential functions of carnitine in metabolism were realized by carnitine which was synthesized endogenously. [source]


    Effects of dietary l -carnitine supplements on growth and body composition in beluga sturgeon (Huso huso) juveniles

    JOURNAL OF APPLIED ICHTHYOLOGY, Issue 6 2008
    M. Mohseni
    Summary The effects of dietary l -carnitine on growth performance, whole body composition and feed utilization were studied in beluga, Huso huso. Fish were randomly allocated in 15 tanks (30 fish per tank) and triplicate groups were fed to satiety during 84 days one of five isonitrogenous (41% CP) and isoenergetic (20 MJ kg,1) diets, each differing in l -carnitine content [0 (control), 300, 600, 900 and 1200 mg kg,1 diet]. At the end of the trial, fish grew from 19- to 23-fold in weight, from 8.4 g to a maximum of 191 g. Fish fed 300,600 mg l -carnitine had the highest specific growth rate (SGR, 3.69 and 3.72% day,1) and protein efficiency ratio (PER, 0.95 and 0.99), and the lowest feed conversion ratio (FCR, 1.4 and 1.3) than the other groups (P < 0.0001). SGR, PER and FCR were the poorest for fish fed 1200 mg l -carnitine, while fish fed the unsupplemented and 900 mg l -carnitine supplemented diet showed intermediate performance. Body lipid concentration decreased significantly from 5.8 to 5.1% (P < 0.0001) with dietary l -carnitine supplementation increasing from 0 to 300 mg. Energy content was significantly lower in fish fed the 900 and 1200 mg l -carnitine diet (5.8 MJ kg,1), when compared with the other treatment groups (6.4,6.6 MJ kg,1). The results indicated that feeding sturgeon on diets supplemented with 300 mg l -carnitine kg,1 diet improved growth performance, and stimulated protein-sparing effects from lipids. [source]


    Changes in amino acid composition in the tissues of African catfish (Clarias gariepinus) as a consequence of dietary L-carnitine supplements

    JOURNAL OF APPLIED ICHTHYOLOGY, Issue 3 2002
    R. O. A. Ozório
    A study was undertaken to examine the effect of different amounts of dietary lysine (13 and 21 g kg,1 diet), lipid (80 and 160 g kg,1 diet) and L -carnitine (0.2 and 1.0 g kg,1 diet) on growth performance, proximate composition and amino acid metabolism of the African catfish (Clarias gariepinus). Juvenile African catfish (23 ± 1.5 g/fish) were stocked into 70-L aquaria (16 aquaria, 28 fish/aquarium) connected to a recirculation system during a maximum period of 74 days. All groups were fed at a level of 24 g kg,0.8 day,1 in an experiment run at pair feeding. Animals receiving 1.0 g carnitine accumulated up to six times more carnitine in their tissues than animals receiving 0.2 g (P < 0.05). Acyl-carnitine and free L -carnitine levels increased in the whole body and in tissues. Dietary L -carnitine supplements increased protein-to-fat ratios in the body, but did not affect growth rate. Protein-to-fat ratios were only affected when the biosynthesis capacity of L -carnitine was restricted due to low lysine levels and when there was a shortage of dietary fat. When lysine was offered at 21 g kg,1 feed, dietary L -carnitine supplements did not affect the amino acid concentrations of body tissues. Dietary L -carnitine supplements raised the concentration of glutamic acid,>,aspartic acid,>,glycine > alanine > arginine > serine > threonine in skeletal muscle tissue (P < 0.05). Total amino acid concentration in muscle and liver tissues (dry-matter basis) increased from 506 to 564 and from 138 to 166 mg g,1, respectively, when diets were offered with high L -carnitine, low lysine and low fat levels. These data suggest that dietary L -carnitine supplementation may increase fatty acid oxidation and possibly decrease amino acid combustion for energy. [source]


    OCTN3: A Na+ -independent L -carnitine transporter in enterocytes basolateral membrane

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005
    J.M. Durán
    L -carnitine transport has been measured in enterocytes and basolateral membrane vesicles (BLMV) isolated from chicken intestinal epithelia. In the nominally Na+ -free conditions chicken enterocytes take up L -carnitine until the cell to medium L -carnitine ratio is 1. This uptake was inhibited by L -carnitine, D -carnitine, ,-butyrobetaine, acetylcarnitine, tetraethylammonium (TEA), and betaine. L - 3H-carnitine uptake into BLMV showed no overshoot, and it was (i) Na+ -independent, (ii) trans-stimulated by intravesicular L -carnitine, and (iii) cis-inhibited by TEA and cold L -carnitine. L - 3H-carnitine efflux from L - 3H-carnitine preloaded enterocytes was also Na+ -independent, and trans-stimulated by L -carnitine, D -carnitine, ,-butyrobetaine, acetylcarnitine, TEA, and betaine. Both, uptake and efflux of L -carnitine were inhibited by verapamil and unaffected by either extracellular pH or palmitoyl- L -carnitine. RT-PCR with specific primers for the mouse OCTN3 transporter revealed the existence of OCTN3 mRNA in mouse intestine, which was confirmed by in situ hybridization studies. Immunohystochemical analysis showed that OCTN3 protein was mainly associated with the basolateral membrane of rat and chicken enterocytes, whereas OCTN2 was detected at the apical membrane. In conclusion, the results demonstrate for the first time that (i) mammalian small intestine expresses OCTN3 mRNA along the villus and (ii) that OCTN3 protein is located in the basolateral membrane. They also suggest that OCTN3 could mediate the passive, Na+ and pH-independent L -carnitine transport activity measured in the three experimental conditions. © 2004 Wiley-Liss, Inc. [source]


    Acetyl -l- carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission

    AGING CELL, Issue 4 2010
    Vanessa Palermo
    Summary In this work we report that carnitines, in particular acetyl -l- carnitine (ALC), are able to prolong the chronological aging of yeast cells during the stationary phase. Lifespan extension is significantly reduced in yca1 mutants as well in rho0 strains, suggesting that the protective effects pass through the Yca1 caspase and mitochondrial functions. ALC can also prevent apoptosis in pro-apoptotic mutants, pointing to the importance of mitochondrial functions in regulating yeast apoptosis and aging. We also demonstrate that ALC attenuates mitochondrial fission in aged yeast cells, indicating a correlation between its protective effect and this process. Our findings suggest that ALC, used as therapeutic for stroke, myocardial infarction and neurodegenerative diseases, besides the well-known anti-oxidant effects, might exert protective effects also acting on mitochondrial morphology. [source]


    Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants

    AGING CELL, Issue 4 2009
    Sang-Kyu Park
    Summary We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S. Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl- l -carnitine and tempol were as effective as CR in the heart, and ,-lipoic acid and coenzyme Q10 were as effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis. [source]